Lipid raft

Last updated
Lipid raft organization, region (1) is a standard lipid bilayer, while region (2) is a lipid raft. Lipid raft organisation scheme.svg
Lipid raft organization, region (1) is a standard lipid bilayer, while region (2) is a lipid raft.

The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. [1] [2] [3] Their existence in cellular membranes remains controversial. Indeed, Kervin and Overduin imply that lipid rafts are misconstrued protein islands, which they propose form through a proteolipid code. [4] Nonetheless, it has been proposed that they are specialized membrane microdomains which compartmentalize cellular processes by serving as organising centers for the assembly of signaling molecules, allowing a closer interaction of protein receptors and their effectors to promote kinetically favorable interactions necessary for the signal transduction. [5] Lipid rafts influence membrane fluidity and membrane protein trafficking, thereby regulating neurotransmission and receptor trafficking. [3] [6] Lipid rafts are more ordered and tightly packed than the surrounding bilayer, but float freely within the membrane bilayer. [7] Although more common in the cell membrane, lipid rafts have also been reported in other parts of the cell, such as the Golgi apparatus and lysosomes.

Contents

Properties

Space-filling models of sphingomyelin (a) and cholesterol (b) Space-Filling Model Sphingomyelin and Cholesterol.jpg
Space-filling models of sphingomyelin (a) and cholesterol (b)

One key difference between lipid rafts and the plasma membranes from which they are derived is lipid composition. Research has shown that lipid rafts contain 3 to 5-fold the amount of cholesterol found in the surrounding bilayer. [8] Also, lipid rafts are enriched in sphingolipids such as sphingomyelin, which is typically elevated by 50% compared to the plasma membrane. To offset the elevated sphingolipid levels, phosphatidylcholine levels are decreased which results in similar choline-containing lipid levels between the rafts and the surrounding plasma membrane. Cholesterol interacts preferentially, although not exclusively, with sphingolipids due to their structure and the saturation of the hydrocarbon chains. Although not all of the phospholipids within the raft are fully saturated, the hydrophobic chains of the lipids contained in the rafts are more saturated and tightly packed than the surrounding bilayer. [6] Cholesterol is the dynamic "glue" that holds the raft together. [3] Due to the rigid nature of the sterol group, cholesterol partitions preferentially into the lipid rafts where acyl chains of the lipids tend to be more rigid and in a less fluid state. [6] One important property of membrane lipids is their amphipathic character. Amphipathic lipids have a polar, hydrophilic head group and a non-polar, hydrophobic region. [9] The figure to the right shows the inverted cone-like shape of sphingomyelin and the cone-like shape of cholesterol based on the area of space occupied by the hydrophobic and hydrophilic regions. Cholesterol can pack in between the lipids in rafts, serving as a molecular spacer and filling any voids between associated sphingolipids. [9]

Rietveld & Simons related lipid rafts in model membranes to the immiscibility of ordered (Lo phase) and disordered (Ld or Lα phase) liquid phases. [10] The cause of this immiscibility is uncertain, but the immiscibility is thought to minimize the free energy between the two phases. Studies have shown there is a difference in thickness of the lipid rafts and the surrounding membrane which results in hydrophobic mismatch at the boundary between the two phases. This phase height mismatch has been shown to increase line tension which may lead to the formation of larger and more circular raft platforms to minimize the energetic cost of maintaining the rafts as a separate phase. Other spontaneous events, such as curvature of the membrane and fusing of small rafts into larger rafts, can also minimize line tension. [6]

By one early definition of lipid rafts, lipid rafts differ from the rest of the plasma membrane. In fact, researchers [11] [ who? ] have hypothesized that the lipid rafts can be extracted from a plasma membrane. The extraction would take advantage of lipid raft resistance to non-ionic detergents, such as Triton X-100 or Brij-98 at low temperatures (e.g., 4 °C). When such a detergent is added to cells, the fluid membrane will dissolve while the lipid rafts may remain intact and could be extracted.[ citation needed ]

Because of their composition and detergent resistance, lipid rafts are also called detergent-insoluble glycolipid-enriched complexes (GEMs) or DIGs [12] or Detergent Resistant Membranes (DRMs). However the validity of the detergent resistance methodology of membranes has recently been called into question due to ambiguities in the lipids and proteins recovered and the observation that they can also cause solid areas to form where there were none previously. [13]

Function

Mediation of substrate presentation. Lipid rafts localize palmitoylated proteins away from the disordered region of the plasma membrane. [14] Disruption of palmitate mediated localization then allows for exposure of a protein to its binding partner or substrate in the disordered region, an activation mechanism termed substrate presentation. For example, a protein is often palmitoylated and binds phosphatidylinositol 4,5-biphosphate (PIP2). PIP2 is polyunsaturated and does not reside in lipid rafts. When the levels of PIP2 increase in the plasma membrane, the protein trafficks to PIP2 clusters where it can be activated directly by PIP2 (or another molecule that associates with PIP2). [15] [16]

It is probable that other functions exist.

History

Until 1982, it was widely accepted that phospholipids and membrane proteins were randomly distributed in cell membranes, according to the Singer-Nicolson fluid mosaic model, published in 1972. [6] [17] However, membrane microdomains were postulated in the 1970s using biophysical approaches by Stier & Sackmann [18] and Klausner & Karnovsky. [19] These microdomains were attributed to the physical properties and organization of lipid mixtures by Stier & Sackmann and Israelachvili et al. [20] In 1974, the effects of temperature on membrane behavior had led to the proposal of "clusters of lipids" in membranes and by 1975, data suggested that these clusters could be "quasicrystalline" regions within the more freely dispersed liquid crystalline lipid molecule. In 1978, X-Ray diffraction studies led to further development of the "cluster" idea defining the microdomains as "lipids in a more ordered state". Karnovsky and co-workers formalized the concept of lipid domains in membranes in 1982. Karnovsky's studies showed heterogeneity in the lifetime decay of 1,6-diphenyl-1,3,5-hexatriene, which indicated that there were multiple phases in the lipid environment of the membrane. [6] One type of microdomain is constituted by cholesterol and sphingolipids. They form because of the segregation of these lipids into a separate phase, demonstrated by Biltonen and Thompson and their coworkers. [21] These microdomains (‘rafts’) were shown to exist also in cell membranes. [22] Later, Kai Simons at the European Molecular Biology Laboratory (EMBL) in Germany and Gerrit van Meer from the University of Utrecht, Netherlands refocused interest on these membrane microdomains, enriched with lipids and cholesterol, glycolipids, and sphingolipids, present in cell membranes. [23] Subsequently, they called these microdomains, lipid "rafts". The original concept of rafts was used as an explanation for the transport of cholesterol from the trans Golgi network to the plasma membrane. The idea was more formally developed in 1997 by Simons and Ikonen. [24] At the 2006 Keystone Symposium of Lipid Rafts and Cell Function, lipid rafts were defined as "small (10-200nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein interactions" In recent years, lipid raft studies have tried to address many of the key issues that cause controversy in this field, including the size and lifetime of rafts.

Other questions yet to be answered include:

Common types

Two types of lipid rafts have been proposed: planar lipid rafts (also referred to as non-caveolar, or glycolipid, rafts) and caveolae. Planar rafts are defined as being continuous with the plane of the plasma membrane (not invaginated) and by their lack of distinguishing morphological features. Caveolae, on the other hand, are flask shaped invaginations of the plasma membrane that contain caveolin proteins and are the most readily-observed structures in lipid rafts. Caveolins are widely expressed in the brain, micro-vessels of the nervous system, endothelial cells, astrocytes, oligodendrocytes, Schwann cells, dorsal root ganglia and hippocampal neurons. Planar rafts contain flotillin proteins and are found in neurons where caveolae are absent. Both types have similar lipid composition (enriched in cholesterol and sphingolipids). Flotillin and caveolins can recruit signaling molecules into lipid rafts, thus playing an important role in neurotransmitter signal transduction. It has been proposed that these microdomains spatially organize signaling molecules to promote kinetically favorable interactions which are necessary for signal transduction. Conversely, these microdomains can also separate signaling molecules, inhibiting interactions and dampening signaling responses. [25]

Role in signal transduction

The specificity and fidelity of signal transduction are essential for cells to respond efficiently to changes in their environment. This is achieved in part by the differential localization of proteins that participate in signalling pathways. In the plasma membrane, one approach of compartmentalization utilizes lipid rafts. [26]

One reasonable way to consider lipid rafts is that small rafts can form concentrating platforms after ligand binding activation for individual receptors. [27] Lipid rafts have been found by researchers to be involved in many signal transduction processes, such as Immunoglobulin E signalling, T cell antigen receptor signalling, B cell antigen receptor signalling, EGF receptor signalling, insulin receptor signalling and so on. In order to illustrate these principles, detailed examples of signalling pathways that involve lipid rafts are described below.

Epidermal growth factor signaling

Epidermal growth factor (EGF) binds to EGF receptor, also known as HER-1 or ErbB1, to initiate transmembrane signaling. Lipid rafts have been suggested to play a bipartite role in this process. Certain aspects of lipid rafts inhibit EGF receptor function:

At the same time lipid rafts seem to be necessary for or potentiate transmembrane signaling:

Immunoglobulin E signaling

Components for IgE signalling Components for IgE signalling.jpeg
Components for IgE signalling
IgE signalling process IgE signalling process.jpeg
IgE signalling process

Immunoglobulin E (IgE) signaling is the first convincingly demonstrated lipid rafts involving signaling process. [39] [40] [41] Evidence for this fact includes decreased solubility of Fc-epsilon receptors (FcεR) in Triton X-100 from steady state to crosslinking state, [39] formation of patches large enough to be visualized by fluorescence microscopy from gangliosides and GPI-anchored proteins, [42] [43] abolition of IgE signaling by surface cholesterol depletion with methyl-β-cyclodextrin [44] and so on. This signaling pathway can be described as follows: IgE first binds to Fc-epsilon receptors (FcεR) residing in the plasma membrane of mast cells and basophils through its Fc segment. FcεR is a tetramer consist of one α, one β and two γ chains. [41] It is monomeric and binds one IgE molecule. The α chain binds IgE and the other three chains contain immune receptor tyrosine-based activation motifs (ITAM). Then oligomeric antigens bind to receptor-bound IgE to crosslink two or more of these receptors. This crosslinking then recruits doubly acylated non-receptor Src-like tyrosine kinase Lyn to phosphorylate ITAMs. After that, Syk family tyrosine kinases bind these phosphotyrosine residues of ITAMs to initiate the signaling cascade. [39] [40] Syk can, in turn, activate other proteins such as LAT. Through crosslinking, LAT can recruit other proteins into the raft and further amplify the signal. [45]

T-cell antigen receptor signaling

Components for T-cell antigen receptor signalling Components for T-cell antigen receptor signalling.jpeg
Components for T-cell antigen receptor signalling
T-cell antigen receptor signalling process T-cell antigen receptor signalling process.jpeg
T-cell antigen receptor signalling process

T cell antigen receptor (TCR) is a molecule found on the surface of T lymphocytes (T cells). It is composed of αβ-heterodimers, CD3 (γδε) complex and ξ-homodimer. The α- and β- subunits contains extracellular binding sites for peptides that are presented by the major histocompatibility complex (MHC) class I and class II proteins on the surface of antigen presenting cells (APCs). The CD3 and ξ- subunits contain cytoplasmic ITAM motifs. During the signaling process, MHCs binding to TCRs brings two or more receptors together. This crosslinking, similar to IgE signaling, then recruit doubly acylated non-receptor Src-like tyrosine kinases to phosphorylate ITAM tyrosine residues. In addition to recruiting Lyn, TCR signaling also recruits Fyn. [26] [46] Following this procedure, ZAP-70 (which is also different with IgE signalling) binds to phosphorylated ITAMs, which leads to its own activation and LAT activation. LAT activation is the source of signal amplification. Another difference between IgE and T cell antigen receptor signalling is that Lck activation by TCR could result in more severe raft clustering [47] [48] thus more signal amplification. One possible mechanism of down-regulating this signaling involves the binding of cytosolic kinase Csk to the raft associated protein CBP. Csk may then suppress the Src-family kinases through phosphorylation. [49]

B-cell antigen receptor signaling

B cell antigen receptor (BCR) is a complex between a membrane bound Ig (mIg) molecule and a disulfide-linked Igα- Igβ heterodimer of two polypeptides. [50] Igα and Igβ each contains an amino acid motif, called ITAM, whose sequence is D/ExxYxxL/Ix7YxxL/I.

The process of B cell antigen receptor signalling is similar to Immunoglobulin E signalling and T-cell antigen receptor signalling. It is commonly believed that other than BCR, lipid rafts play an important role in many of the cell surface events involved in B cell activation. Their functions include signaling by BCR, modulation of that signaling by co-receptors, signaling by CD40, endocytosis of antigen bound to the BCR and its routing to late endosomes to facilitate loading of antigen-derived peptides onto class II MHC molecules, routing of those peptide/MHC-II complexes to the cell surface, and their participation in antigen presentation to T cells. [50]

As platforms for virus entry

Viruses, as obligate intracellular parasites, have to involve specific interaction of virus and cellular receptor expressed at the plasma membrane in order to enter cells. Accumulated evidence supports that viruses enter cells via penetration of specific membrane microdomains, including lipid rafts.

Nonenveloped virus

The best studied models of lipid rafts-related nonenveloped viral entry are simian virus 40 (SV40, Papovaviridae) and echovirus type 1 (EV1, Picornaviridae). [51] [52]

SV40 utilizes two different receptors to bind onto cell surface: ganglioside GM1 located in lipid rafts and major histocompatibility (MHC) class I molecule. [51] [52] Binding of SV40 with MHC class I molecules triggers receptor clustering and redistribution. SV40 may recruit more caveolae from the cytoplasm or even new caveolae formed at the site of entry. [52] A cascade of virus-induced signaling events triggered by attachment results in caveolae-mediated endocytosis in about 20 min. [52] In some cell types the virus can enter the caveosomes directly from lipid rafts in non-coated vesicles. [52] [53]

EV1 uses α2β1-integrin as cellular receptor. [51] Multiple integrin heterodimers can bind to the adjacent sites of the virus capsid. [52] Similar to SV40, attachment and binding with cells triggers clustering and relocation of integrin molecules from lipid rafts to the caveolae-like structures. [52] Depletion of cholesterol in lipid rafts inhibits EV1 infection. [51]

There are also viruses that use the non-caveolar raft-mediated endocytosis, such as Echovirus 11 (EV11, picornavirus). However, detailed mechanisms still need to be further characterized. [52]

Enveloped virus

Influenza viruses bind to the cellular receptor sialic acid, which links to glycoconjugate on the cell surface, to initiate endocytosis. After transportation into late endosomes, low-pH-dependent conformation changes of HA induces fusion, and viral ribonucleoprotein complexes (RNP) are released by proton influx of viral ion channel M2 proteins that requires binding with cholesterol. Semliki Forest virus (SFV) and Sindbis virus (SIN) require cholesterol and sphingolipids in target membrane lipid rafts for envelope glycoprotein-mediated membrane fusion and entry. [54] Human T-lymphotropic virus Type I (HTLV-1) enter cells via glucose transporter 1 (GLUT-1). Ebola virus and Marburg virus use folate receptor-α (FRα), which is a GPI-anchored protein, as a cellular receptor. Hepatitis B virus recognizes human complement receptor type 2 (CR2, or known as CD21). Human herpesvirus 6 (HHV-6) binds to human CD46 on host cell surface. All these viral receptors are located in lipid rafts or would be relocated into lipid rafts after infection.

Human Immunodeficiency virus (HIV), as a sexually-transmitted animal virus, must first penetrate a barrier of epithelial cells, who don't express CD4 and chemokine receptors, to establish a productive infection. An alternative receptor for HIV-1 envelope glycoprotein on epithelial cells is glycosphingolipid galactosyl-ceramide (GalCer), which enriches at lipid raft. [55] [56]

SARS-Cov-2

The SARS-CoV-2 virus that causes COVID-19 was shown to enter through endocytosis using lipid rafts. [57] The omicron variant predominantly enters through endocytosis, presumably through lipid rafts. [58] Hydroxychloroquine blocks the entry of SARS-CoV-2 by blocking ACE2 association with enodocytic lipids. [59]

Visualization

One of the primary reasons for the controversy over lipid rafts has stemmed from the challenges of studying lipid rafts in living cells, which are not in thermodynamic equilibrium. [25] Lipid rafts are small microdomains ranging from 10 to 200 nm in size. [6] Due to their size being below the classical diffraction limit of a light microscope, lipid rafts have proved difficult to visualize directly. Currently synthetic membranes are studied; however, there are many drawbacks to using these membranes. First, synthetic membranes have a lower concentration of proteins compared to biomembranes. Also, it is difficult to model membrane-cytoskeletal interactions which are present in biomembranes. Other pitfalls include lack of natural asymmetry and inability to study the membranes in non-equilibrium conditions. [6] [60] Despite this, fluorescence microscopy is used extensively in the field. For example, fluorophores conjugated to cholera-toxin B-subunit, which binds to the raft constituent ganglioside GM1 is used extensively. Also used are lipophilic membrane dyes which either partition between rafts and the bulk membrane, or change their fluorescent properties in response to membrane phase. Laurdan is one of the prime examples of such a dye. Rafts may also be labeled by genetic expression of fluorescent fusion proteins such as Lck-GFP.

Manipulation of cholesterol is one of the most widely used techniques for studying lipid rafts. Sequestration (using filipin, nystatin or amphotericin), depletion and removal (using methyl-B-cyclodextrin) and inhibition of cholesterol synthesis (using HMG-CoA reductase inhibitors) are ways cholesterol are manipulated in lipid raft studies. These studies allow for the observations of effects on neurotransmitter signaling upon reduction of cholesterol levels. [25]

Sharma and colleagues used combination of high resolution imaging and mathematical modeling to provide the view that raft proteins are organized into high density nanoclusters with radii ranging over 5–20 nm. Using measurements of fluorescence resonance energy transfer between the same probes (homo-FRET or fluorescence anisotropy), Sharma and colleagues reported that a fraction (20–40%) of GPI-anchored proteins are organized into high density clusters of 4–5 nm radius, each consisting of a few molecules and different GPI-anchored proteins. [61] To combat the problems of small size and dynamic nature, single particle and molecule tracking using cooled, sensitive CCD cameras and total internal reflection (TIRF) microscopy is coming to prominence. This allows information of the diffusivity of particles in the membrane to be extracted as well as revealing membrane corrals, barriers and sites of confinement. [62]

Other optical techniques are also used: Fluorescence Correlation and Cross-Correlation Spectroscopy (FCS/FCCS) can be used to gain information of fluorophore mobility in the membrane, Fluorescence Resonance Energy Transfer (FRET) can detect when fluorophores are in close proximity and optical tweezer techniques can give information on membrane viscosity. [25]

Not only optical techniques, but also scanning probe techniques like atomic force microscopy (AFM) or Scanning Ion Conductance Microscopy (SICM) can be used to detect the topological and mechanical properties of synthetic lipids [63] or native cell membranes [64] isolated by cell unroofing.

Also used are dual polarisation interferometry, Nuclear Magnetic Resonance (NMR) although fluorescence microscopy remains the dominant technique. In the future it is hoped that super-resolution microscopy such as Stimulated Emission Depletion (STED) [65] or various forms of structured illumination microscopy may overcome the problems imposed by the diffraction limit.

Other techniques used in the analysis of lipid rafts include ELISA, western blotting, and FACS. [66] [67] [1]

Controversy

The role of rafts in cellular signaling, trafficking, and structure has yet to be determined despite many experiments involving several different methods, and their very existence is controversial despite all the above. [68]

Arguments against the existence of lipid rafts include the following:

A first rebuttal to this point suggests that the Lo phase of the rafts is more tightly packed due to the intermolecular hydrogen bonding exhibited between sphingolipids and cholesterol that is not seen elsewhere. [69]

A second argument questions the effectiveness of the experimental design when disrupting lipid rafts. Pike and Miller discuss potential pitfalls of using cholesterol depletion to determine lipid raft function. [70] They noted that most researchers were using acute methods of cholesterol depletion, which disrupt the rafts, but also disrupt another lipid known as PI(4,5)P2. PI(4,5)P2 plays a large role in regulating the cell's cytoskeleton, [71] and disrupting PI(4,5)P2 causes many of the same results as this type of cholesterol depletion, including lateral diffusion of the proteins in the membrane. [72] Because the methods disrupt both rafts and PI(4,5)P2, Kwik et al. concluded that loss of a particular cellular function after cholesterol depletion cannot necessarily be attributed solely to lipid raft disruption, as other processes independent of rafts may also be affected. Finally, while lipid rafts are believed to be connected in some way to proteins, Edidin argues that proteins attract the lipids in the raft by interactions of proteins with the acyl chains on the lipids, and not the other way around. [73]

Related Research Articles

<span class="mw-page-title-main">Endocytosis</span> Cellular process

Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. Endocytosis includes pinocytosis and phagocytosis. It is a form of active transport.

<span class="mw-page-title-main">Signal transduction</span> Cascade of intracellular and molecular events for transmission/amplification of signals

Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events. Most commonly, protein phosphorylation is catalyzed by protein kinases, ultimately resulting in a cellular response. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a signaling pathway.

In biology, caveolae, which are a special type of lipid raft, are small invaginations of the plasma membrane in the cells of many vertebrates. They are the most abundant surface feature of many vertebrate cell types, especially endothelial cells, adipocytes and embryonic notochord cells. They were originally discovered by E. Yamada in 1955.

<span class="mw-page-title-main">Endosome</span> Vacuole to which materials ingested by endocytosis are delivered

Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation or can be recycled back to the cell membrane in the endocytic cycle. Molecules are also transported to endosomes from the trans Golgi network and either continue to lysosomes or recycle back to the Golgi apparatus.

<span class="mw-page-title-main">Glycolipid</span> Class of chemical compounds

Glycolipids are lipids with a carbohydrate attached by a glycosidic (covalent) bond. Their role is to maintain the stability of the cell membrane and to facilitate cellular recognition, which is crucial to the immune response and in the connections that allow cells to connect to one another to form tissues. Glycolipids are found on the surface of all eukaryotic cell membranes, where they extend from the phospholipid bilayer into the extracellular environment.

<span class="mw-page-title-main">Sphingomyelin</span> Class of chemical compounds

Sphingomyelin is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a phosphoethanolamine head group; therefore, sphingomyelins can also be classified as sphingophospholipids. In humans, SPH represents ~85% of all sphingolipids, and typically make up 10–20 mol % of plasma membrane lipids.

In molecular biology, caveolins are a family of integral membrane proteins that are the principal components of caveolae membranes and involved in receptor-independent endocytosis. Caveolins may act as scaffolding proteins within caveolar membranes by compartmentalizing and concentrating signaling molecules. They also induce positive (inward) membrane curvature by way of oligomerization, and hairpin insertion. Various classes of signaling molecules, including G-protein subunits, receptor and non-receptor tyrosine kinases, endothelial nitric oxide synthase (eNOS), and small GTPases, bind Cav-1 through its 'caveolin-scaffolding domain'.

<span class="mw-page-title-main">T-cell receptor</span> Protein complex on the surface of T cells that recognises antigens

The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen peptides is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR.

<span class="mw-page-title-main">Fc receptor</span> Surface protein important to the immune system

In immunology, an Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system. Its name is derived from its binding specificity for a part of an antibody known as the Fc region. Fc receptors bind to antibodies that are attached to infected cells or invading pathogens. Their activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as flaviviruses use Fc receptors to help them infect cells, by a mechanism known as antibody-dependent enhancement of infection.

<span class="mw-page-title-main">Lck</span> Lymphocyte protein

Lck is a 56 kDa protein that is found inside specialized cells of the immune system called lymphocytes. The Lck is a member of Src kinase family (SFK) and is important for the activation of T-cell receptor (TCR) signaling in both naive T cells and effector T cells. The role of Lck is less prominent in the activation or in the maintenance of memory CD8 T cells in comparison to CD4 T cells. In addition, the constitutive activity of the mouse Lck homolog varies among memory T cell subsets. It seems that in mice, in the effector memory T cell (TEM) population, more than 50% of Lck is present in a constitutively active conformation, whereas less than 20% of Lck is present as active form in central memory T cells. These differences are due to differential regulation by SH2 domain–containing phosphatase-1 (Shp-1) and C-terminal Src kinase.

<span class="mw-page-title-main">B-cell receptor</span> Transmembrane protein on the surface of a B cell

The B-cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B-cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 transmembrane receptor protein, and is typically located on the outer surface of these lymphocyte cells. Through biochemical signaling and by physically acquiring antigens from the immune synapses, the BCR controls the activation of the B cell. B cells are able to gather and grab antigens by engaging biochemical modules for receptor clustering, cell spreading, generation of pulling forces, and receptor transport, which eventually culminates in endocytosis and antigen presentation. B cells' mechanical activity adheres to a pattern of negative and positive feedbacks that regulate the quantity of removed antigen by manipulating the dynamic of BCR–antigen bonds directly. Particularly, grouping and spreading increase the relation of antigen with BCR, thereby proving sensitivity and amplification. On the other hand, pulling forces delinks the antigen from the BCR, thus testing the quality of antigen binding.

<span class="mw-page-title-main">Receptor tyrosine kinase</span> Class of enzymes

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non-receptor tyrosine kinases which do not possess transmembrane domains.

<span class="mw-page-title-main">Linker for activation of T cells</span> Protein-coding gene in the species Homo sapiens

The Linker for activation of T cells, also known as linker of activated T cells or LAT, is a protein involved in the T-cell antigen receptor signal transduction pathway which in humans is encoded by the LAT gene. Alternative splicing results in multiple transcript variants encoding different isoforms.

<span class="mw-page-title-main">CBL (gene)</span> Mammalian gene

Cbl is a mammalian gene family. CBL gene, a part of the Cbl family, encodes the protein CBL which is an E3 ubiquitin-protein ligase involved in cell signalling and protein ubiquitination. Mutations to this gene have been implicated in a number of human cancers, particularly acute myeloid leukaemia.

<span class="mw-page-title-main">Caveolin 1</span> Protein-coding gene in the species Homo sapiens

Caveolin-1 is a protein that in humans is encoded by the CAV1 gene.

<span class="mw-page-title-main">FLOT2</span> Protein-coding gene in the species Homo sapiens

Flotillin-2 is a protein that in humans is encoded by the FLOT2 gene. Flotillin 2 (flot-2) is a highly conserved protein isolated from caveolae/lipid raft domains that tether growth factor receptors linked to signal transduction pathways. Flot-2 binds to PAR-1, a known upstream mediator of major signal transduction pathways implicated in cell growth and metastasis, and may influence tumour progression.

Potocytosis is a type of receptor-mediated endocytosis in which small molecules are transported across the plasma membrane of a cell. The molecules are transported by caveolae and are deposited directly into the cytosol.

<span class="mw-page-title-main">Cell surface receptor</span> Class of ligand activated receptors localized in surface of plama cell membrane

Cell surface receptors are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving extracellular molecules. They are specialized integral membrane proteins that allow communication between the cell and the extracellular space. The extracellular molecules may be hormones, neurotransmitters, cytokines, growth factors, cell adhesion molecules, or nutrients; they react with the receptor to induce changes in the metabolism and activity of a cell. In the process of signal transduction, ligand binding affects a cascading chemical change through the cell membrane.

Substrate presentation is a biological process that activates a protein. The protein is sequestered away from its substrate and then activated by release and exposure of the protein to its substrate. A substrate is typically the substance on which an enzyme acts but can also be a protein surface to which a ligand binds. The substrate is the material acted upon. In the case of an interaction with an enzyme, the protein or organic substrate typically changes chemical form. Substrate presentation differs from allosteric regulation in that the enzyme need not change its conformation to begin catalysis. Substrate presentation is best described for nanoscopic distances (<100 nm).

<span class="mw-page-title-main">Cholesterol signaling</span>

Cholesterol is a cell signaling molecule that is highly regulated in eukaryotic cell membranes. In human health, its effects are most notable in inflammation, metabolic syndrome, and neurodegeneration. At the molecular level, cholesterol primarily signals by regulating clustering of saturated lipids and proteins that depend on clustering for their regulation.

References

  1. 1 2 Thomas, Sunil; Preda-Pais, Anca; Casares, Sofia; Brumeanu, Teodor-D (2004). "Analysis of lipid rafts in T cells". Molecular Immunology. 41 (4): 399–409. doi:10.1016/j.molimm.2004.03.022. PMID   15163537.
  2. ↑ Thomas, Sunil; Kumar S., Rajeev; Brumeanu, Teodor−D. (2004). "Role of lipid rafts in T cells". Archivum Immunologiae et Therapiae Experimentalis. 52 (4): 215–24. PMID   15467486.
  3. 1 2 3 Korade, Zeljka; Kenworthy, Anne K. (2008). "Lipid rafts, cholesterol, and the brain". Neuropharmacology. 55 (8): 1265–73. doi:10.1016/j.neuropharm.2008.02.019. PMC   2638588 . PMID   18402986.
  4. ↑ Kervin, TA; Overduin, M (27 February 2024). "Membranes are functionalized by a proteolipid code". BMC Biology. 22 (1): 46. doi: 10.1186/s12915-024-01849-6 . PMC   10898092 . PMID   38414038.
  5. ↑ Alves, Anna Carolina Schneider; Dias, Reinaldo Antonio; Kagami, Luciano Porto; Neves, Gustavo Machado das; Torres, Fernando Cidade; Eifler-Lima, Vera Lucia; Carvalho, Ivone; Kawano*, Carolina de Miranda Silva and Daniel Fabio (2018-05-31). "Beyond the". Current Medicinal Chemistry. 25 (18): 2082–2104. doi:10.2174/0929867325666180111100601. PMID   29332565.
  6. 1 2 3 4 5 6 7 8 9 Pike, L. J. (2008). "The challenge of lipid rafts". The Journal of Lipid Research. 50 (Suppl): S323–8. doi: 10.1194/jlr.R800040-JLR200 . PMC   2674732 . PMID   18955730.
  7. ↑ Simons, Kai; Ehehalt, Robert (2002). "Cholesterol, lipid rafts, and disease". Journal of Clinical Investigation. 110 (5): 597–603. doi:10.1172/JCI16390. PMC   151114 . PMID   12208858.
  8. ↑ Laura, Anchisi; Sandra Dessi; Alessandra Pani; Antonella Mandas (25 November 2012). "Cholesterol homeostasis: a key to prevent or slow down neurodegeneration". Frontiers in Physiology. 3: 486. doi: 10.3389/fphys.2012.00486 . PMC   3539713 . PMID   23316166.
  9. 1 2 Fantini, Jacques; Garmy, Nicolas; Mahfoud, Radhia; Yahi, Nouara (2004). "Lipid rafts: Structure, function and role in HIV, Alzheimer's and prion diseases". Expert Reviews in Molecular Medicine. 4 (27): 1–22. doi:10.1017/S1462399402005392. PMID   14987385. S2CID   2638429.
  10. ↑ Rietveld, Anton; Simons, Kai (1998). "The differential miscibility of lipids as the basis for the formation of functional membrane rafts". Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes. 1376 (3): 467–79. doi:10.1016/S0304-4157(98)00019-7. PMID   9805010.
  11. ↑ Radeva, Galina; Sharom, Frances J. (2004-05-15). "Isolation and characterization of lipid rafts with different properties from RBL-2H3 (rat basophilic leukaemia) cells". Biochemical Journal. 380 (1): 219–230. doi:10.1042/bj20031348. ISSN   0264-6021. PMC   1224147 . PMID   14769131.
  12. ↑ Fivaz, Marc; Abrami, Laurence; Van Der Goot, F.Gisou (1999). "Landing on lipid rafts". Trends in Cell Biology. 9 (6): 212–3. doi:10.1016/S0962-8924(99)01567-6. PMID   10354632.
  13. ↑ Heerklotz, H. (2002). "Triton Promotes Domain Formation in Lipid Raft Mixtures". Biophysical Journal. 83 (5): 2693–701. Bibcode:2002BpJ....83.2693H. doi:10.1016/S0006-3495(02)75278-8. PMC   1302353 . PMID   12414701.
  14. ↑ Levental, I; Lingwood, D; Grzybek, M; Coskun, U; Simons, K (21 December 2010). "Palmitoylation regulates raft affinity for the majority of integral raft proteins". Proceedings of the National Academy of Sciences of the United States of America. 107 (51): 22050–4. Bibcode:2010PNAS..10722050L. doi: 10.1073/pnas.1016184107 . PMC   3009825 . PMID   21131568.
  15. ↑ Petersen, EN; Chung, HW; Nayebosadri, A; Hansen, SB (15 December 2016). "Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D." Nature Communications. 7: 13873. Bibcode:2016NatCo...713873P. doi:10.1038/ncomms13873. PMC   5171650 . PMID   27976674.
  16. ↑ Robinson, CV; Rohacs, T; Hansen, SB (September 2019). "Tools for Understanding Nanoscale Lipid Regulation of Ion Channels". Trends in Biochemical Sciences. 44 (9): 795–806. doi:10.1016/j.tibs.2019.04.001. PMC   6729126 . PMID   31060927.
  17. ↑ Singer, S. J.; Nicolson, Garth L. (1972). "The Fluid Mosaic Model of the Structure of Cell Membranes". Science. 175 (4023): 720–31. Bibcode:1972Sci...175..720S. doi:10.1126/science.175.4023.720. PMID   4333397. S2CID   83851531.
  18. ↑ Stier, A.; Sackmann, E. (1973). "Spin labels as enzyme substrates Heterogeneous lipid distribution in liver microsomal membranes". Biochimica et Biophysica Acta (BBA) - Biomembranes. 311 (3): 400–8. doi:10.1016/0005-2736(73)90320-9. PMID   4354130.
  19. ↑ Karnovsky, Morris J.; Kleinfeld, Alan M.; Hoover, Richard L.; Klausner, Richard D. (1982). "The concept of lipid domains in membranes". The Journal of Cell Biology. 94 (1): 1–6. doi:10.1083/jcb.94.1.1. PMC   2112185 . PMID   6889603.
  20. ↑ Israelachvili, J. N.; Marčelja, S.; Horn, R. G. (2009). "Physical principles of membrane organization". Quarterly Reviews of Biophysics. 13 (2): 121–200. doi:10.1017/S0033583500001645. hdl: 10536/DRO/DU:30041475 . PMID   7015403. S2CID   33387523.
  21. ↑ Estep, T. N.; Mountcastle, D. B.; Barenholz, Y.; Biltonen, R. L.; Thompson, T. E. (1979). "Thermal behavior of synthetic sphingomyelin-cholesterol dispersions". Biochemistry. 18 (10): 2112–7. doi:10.1021/bi00577a042. PMID   435470.
  22. ↑ Goodsaid-Zalduondo, F.; Rintoul, D. A.; Carlson, J. C.; Hansel, W. (1982). "Luteolysis-Induced Changes in Phase Composition and Fluidity of Bovine Luteal Cell Membranes". Proceedings of the National Academy of Sciences of the United States of America. 79 (14): 4332–6. Bibcode:1982PNAS...79.4332G. doi: 10.1073/pnas.79.14.4332 . JSTOR   12587. PMC   346665 . PMID   6956862.
  23. ↑ Simons, Kai; Van Meer, Gerrit (1988). "Lipid sorting in epithelial cells". Biochemistry. 27 (17): 6197–202. doi:10.1021/bi00417a001. hdl: 1874/293951 . PMID   3064805.
  24. ↑ Simons, Kai; Ikonen, Elina (1997). "Functional rafts in cell membranes". Nature. 387 (6633): 569–72. Bibcode:1997Natur.387..569S. doi:10.1038/42408. PMID   9177342. S2CID   4359503.
  25. 1 2 3 4 Allen, John A.; Halverson-Tamboli, Robyn A.; Rasenick, Mark M. (2006). "Lipid raft microdomains and neurotransmitter signalling". Nature Reviews Neuroscience. 8 (2): 128–40. doi:10.1038/nrn2059. PMID   17195035. S2CID   2098892.
  26. 1 2 Janes, Peter W.; Ley, Steven C.; Magee, Anthony I.; Kabouridis, Panagiotis S. (2000). "The role of lipid rafts in T cell antigen receptor (TCR) signalling". Seminars in Immunology. 12 (1): 23–34. doi:10.1006/smim.2000.0204. PMID   10723795.
  27. ↑ Schmitz, Gerd; Grandl, Margot (2008). "Update on lipid membrane microdomains". Current Opinion in Clinical Nutrition and Metabolic Care. 11 (2): 106–12. doi:10.1097/MCO.0b013e3282f44c2c. PMID   18301084. S2CID   13102246. Archived from the original on 2022-04-22. Retrieved 2019-11-24.
  28. ↑ Miljan, Erik A; Bremer, Eric G. (2002). "Regulation of growth factor receptors by gangliosides". Sci STKE. 2002 (160): RE15. doi:10.1126/stke.2002.160.re15. PMID   12454318. S2CID   84509111.
  29. ↑ Coskun, Ünal; Grzybek, Michal; Drechsel, David; Simons, Kai (2011). "Regulation of human EGF receptor by lipids". Proc Natl Acad Sci U S A. 108 (22): 9044–8. Bibcode:2011PNAS..108.9044C. doi: 10.1073/pnas.1105666108 . PMC   3107302 . PMID   21571640.
  30. 1 2 Kovács, Tamás; Batta, Gyula; Zákány, Florina; Szöllősi, János; Nagy, Peter (2017). "The dipole potential correlates with lipid raft markers in the plasma membrane of living cells". J Lipid Res. 58 (8): 1681–1691. doi: 10.1194/jlr.M077339 . PMC   5538289 . PMID   28607008.
  31. 1 2 3 Kovács, Tamás; Batta, Gyula; Hajdu, Tímea; Szabó, Ágnes; Váradi, Tímea; Zákány, Florina; Csomós, István; Szöllősi, János; Nagy, Peter (2016). "The Dipole Potential Modifies the Clustering and Ligand Binding Affinity of ErbB Proteins and Their Signaling Efficiency". Sci Rep. 6: 35850. Bibcode:2016NatSR...635850K. doi:10.1038/srep35850. PMC   5075772 . PMID   27775011.
  32. ↑ Roepstorff, Kirstine; Thomsen, Peter; Sandvig, Kirsten; van Deurs, Deurs (2002). "Sequestration of epidermal growth factor receptors in non-caveolar lipid rafts inhibits ligand binding". J Biol Chem. 277 (21): 18954–60. doi: 10.1074/jbc.M201422200 . PMID   11886870.
  33. ↑ Mineo, Chieko; Gill, Gordon N.; Anderson, Richard G.W. (1999). "Regulated migration of epidermal growth factor receptor from caveolae". J Biol Chem. 274 (43): 30636–43. doi: 10.1074/jbc.274.43.30636 . PMID   10521449.
  34. ↑ Lambert, Sylviane; Vind-Kezunovic, Dina; Karvinen, Susanna; Gniadecki, Robert (May 2006). "Ligand-Independent Activation of the EGFR by Lipid Raft Disruption". Journal of Investigative Dermatology. 126 (5): 954–962. doi: 10.1038/sj.jid.5700168 . PMID   16456534.
  35. ↑ Nagy, Peter; Vereb, György; Sebestyén, Zsolt; Horváth, Gábor; Lockett, Stephen J.; Damjanovich, Sándor; Park, John W.; Jovin, Thomas M.; Szöllősi, János (2002-11-15). "Lipid rafts and the local density of ErbB proteins influence the biological role of homo- and heteroassociations of ErbB2". Journal of Cell Science. 115 (22): 4251–4262. doi: 10.1242/jcs.00118 . hdl: 2437/80814 . ISSN   0021-9533. PMID   12376557.
  36. ↑ Hofman, Erik G.; Ruonala, Mika O.; Bader, Arjen N.; Heuvel, Dave van den; Voortman, Jarno; Roovers, Rob C.; Verkleij, Arie J.; Gerritsen, Hans C.; Henegouwen, Paul M. P. van Bergen en (2008-08-01). "EGF induces coalescence of different lipid rafts". Journal of Cell Science. 121 (15): 2519–2528. doi: 10.1242/jcs.028753 . ISSN   0021-9533. PMID   18628305.
  37. ↑ FILIPP, D (2004). "Lipid rafts: resolution of the ?fyn problem??". Molecular Immunology. 41 (6–7): 645–656. doi:10.1016/j.molimm.2004.04.011. PMID   15220001.
  38. ↑ Irwin, Mary E.; Mueller, Kelly L.; Bohin, Natacha; Ge, Yubin; Boerner, Julie L. (2011-09-01). "Lipid raft localization of EGFR alters the response of cancer cells to the EGFR tyrosine kinase inhibitor gefitinib". Journal of Cellular Physiology. 226 (9): 2316–2328. doi:10.1002/jcp.22570. ISSN   1097-4652. PMC   3103760 . PMID   21660955.
  39. 1 2 3 Field, Kenneth A.; Holowka, David; Baird, Barbara (1995). "FcɛRI-Mediated Recruitment of p53/56lyn to Detergent- Resistant Membrane Domains Accompanies Cellular Signaling". Proceedings of the National Academy of Sciences of the United States of America. 92 (20): 9201–5. Bibcode:1995PNAS...92.9201F. doi: 10.1073/pnas.92.20.9201 . JSTOR   2368438. PMC   40952 . PMID   7568101.
  40. 1 2 Sheets, Erin D; Holowka, David; Baird, Barbara (1999). "Membrane organization in immunoglobulin E receptor signaling". Current Opinion in Chemical Biology. 3 (1): 95–9. doi: 10.1016/S1367-5931(99)80017-9 . PMID   10021405.
  41. 1 2 Baird, Barbara; Sheets, Erin D; Holowka, David (1999). "How does the plasma membrane participate in cellular signaling by receptors for immunoglobulin E?". Biophysical Chemistry. 82 (2–3): 109–19. doi: 10.1016/S0301-4622(99)00110-6 . PMID   10631794.
  42. ↑ Stauffer, Thomas P.; Meyer, Tobias (1997). "Compartmentalized IgE Receptor-mediated Signal Transduction in Living Cells". The Journal of Cell Biology. 139 (6): 1447–54. doi:10.1083/jcb.139.6.1447. PMC   2132626 . PMID   9396750.
  43. ↑ Holowka, David; Sheets, Erin D.; Baird, Barbara (2000). "Interactions between FcεRI and lipid raft components are regulated by the actin cytoskeleton". Journal of Cell Science. 113 (6): 1009–19. doi:10.1242/jcs.113.6.1009. PMID   10683149.
  44. ↑ Sheets, E. D.; Holowka, D; Baird, B (1999). "Critical Role for Cholesterol in Lyn-mediated Tyrosine Phosphorylation of Fcepsilon RI and Their Association with Detergent-resistant Membranes". The Journal of Cell Biology. 145 (4): 877–87. doi:10.1083/jcb.145.4.877. PMC   2133197 . PMID   10330413.
  45. ↑ Goitsuka, R.; Kanazashi, H; Sasanuma, H; Fujimura, Y; Hidaka, Y; Tatsuno, A; Ra, C; Hayashi, K; Kitamura, D (2000). "A BASH/SLP-76-related adaptor protein MIST/Clnk involved in IgE receptor-mediated mast cell degranulation". International Immunology. 12 (4): 573–80. doi: 10.1093/intimm/12.4.573 . PMID   10744659.
  46. ↑ Langlet, Claire; Bernard, Anne-Marie; Drevot, Philippe; He, Hai-Tao (2000). "Membrane rafts and signaling by the multichain immune recognition receptors". Current Opinion in Immunology. 12 (3): 250–5. doi:10.1016/S0952-7915(00)00084-4. PMID   10781401.
  47. ↑ Zhang, W; Trible, RP; Samelson, LE (1998). "LAT PalmitoylationIts Essential Role in Membrane Microdomain Targeting and Tyrosine Phosphorylation during T Cell Activation". Immunity. 9 (2): 239–46. doi: 10.1016/S1074-7613(00)80606-8 . PMID   9729044.
  48. ↑ Brdička, Tomáš; Černý, Jan; Hořejší, Václav (1998). "T Cell Receptor Signalling Results in Rapid Tyrosine Phosphorylation of the Linker Protein LAT Present in Detergent-Resistant Membrane Microdomains". Biochemical and Biophysical Research Communications. 248 (2): 356–60. doi:10.1006/bbrc.1998.8857. PMID   9675140. S2CID   782789.
  49. ↑ Cooper, Jonathan A.; Cary, Leslie A. (2000). "Molecular switches in lipid rafts". Nature. 404 (6781): 945–947. doi: 10.1038/35010257 . PMID   10801110.
  50. 1 2 Gupta, Neetu; Defranco, Anthony L. (2007). "Lipid rafts and B cell signaling". Seminars in Cell & Developmental Biology. 18 (5): 616–26. doi:10.1016/j.semcdb.2007.07.009. PMC   2169358 . PMID   17719248.
  51. 1 2 3 4 Chazal, Nathalie; Gerlier, Denis (2003). "Virus Entry, Assembly, Budding, and Membrane Rafts". Microbiology and Molecular Biology Reviews. 67 (2): 226–37, table of contents. doi:10.1128/MMBR.67.2.226-237.2003. PMC   156468 . PMID   12794191.
  52. 1 2 3 4 5 6 7 8 Pietiäinen, Vilja M.; Marjomäki, Varpu; Heino, Jyrki; Hyypiä, Timo (2005). "Viral entry, lipid rafts and caveosomes". Annals of Medicine. 37 (6): 394–403. doi: 10.1080/07853890510011976 . PMID   16203612. S2CID   40632761.
  53. ↑ Rajendran, Lawrence; Simons, Kai (2005). "Lipid rafts and membrane dynamics". Journal of Cell Science. 118 (6): 1099–102. doi: 10.1242/jcs.01681 . PMID   15764592.
  54. ↑ Rawat, Satinder S.; Viard, Mathias; Gallo, Stephen A.; Rein, Alan; Blumenthal, Robert; Puri, Anu (2003). "Modulation of entry of enveloped viruses by cholesterol and sphingolipids (Review)". Molecular Membrane Biology. 20 (3): 243–54. doi: 10.1080/0968768031000104944 . PMID   12893532. S2CID   36443978.
  55. ↑ Campbell, S.M; Crowe, S.M; Mak, J (2001). "Lipid rafts and HIV-1: From viral entry to assembly of progeny virions". Journal of Clinical Virology. 22 (3): 217–27. doi:10.1016/S1386-6532(01)00193-7. PMID   11564586.
  56. ↑ Alving, Carl R.; Beck, Zoltan; Karasavva, Nicos; Matyas, Gary R.; Rao, Mangala (2006). "HIV-1, lipid rafts, and antibodies to liposomes: Implications for anti-viral-neutralizing antibodies (Review)". Molecular Membrane Biology. 23 (6): 453–65. doi: 10.1080/09687860600935348 . PMID   17127618. S2CID   38887150.
  57. ↑ Wang, Hao; Yuan, Zixuan; Pavel, Mahmud Arif; Jablonski, Sonia Mediouni; Jablonski, Joseph; Hobson, Robert; Valente, Susana; Reddy, Chakravarthy B.; Hansen, Scott B. (10 May 2020). "The role of high cholesterol in age-related COVID19 lethality". bioRxiv   10.1101/2020.05.09.086249 .
  58. ↑ Meng, B; et al. (March 2022). "Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity". Nature. 603 (7902): 706–714. Bibcode:2022Natur.603..706M. doi:10.1038/s41586-022-04474-x. PMC   8942856 . PMID   35104837.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  59. ↑ Yuan, Zixuan; Pavel, Mahmud Arif; Wang, Hao; Kwachukwu, Jerome C.; Mediouni, Sonia; Jablonski, Joseph Anthony; Nettles, Kendall W.; Reddy, Chakravarthy B.; Valente, Susana T.; Hansen, Scott B. (14 September 2022). "Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture". Communications Biology. 5 (1): 958. doi:10.1038/s42003-022-03841-8. PMC   9472185 . PMID   36104427.
  60. ↑ Jacobson, Ken; Mouritsen, Ole G.; Anderson, Richard G. W. (2007). "Lipid rafts: At a crossroad between cell biology and physics". Nature Cell Biology. 9 (1): 7–14. doi:10.1038/ncb0107-7. PMID   17199125. S2CID   7876073.
  61. ↑ Sharma, Pranav; Varma, Rajat; Sarasij, R.C; Ira; Gousset, Karine; Krishnamoorthy, G; Rao, Madan; Mayor, Satyajit (2004). "Nanoscale Organization of Multiple GPI-Anchored Proteins in Living Cell Membranes". Cell. 116 (4): 577–89. doi: 10.1016/S0092-8674(04)00167-9 . PMID   14980224.
  62. ↑ Ritchie, Ken; Shan, Xiao-Yuan; Kondo, Junko; Iwasawa, Kokoro; Fujiwara, Takahiro; Kusumi, Akihiro (2005). "Detection of Non-Brownian Diffusion in the Cell Membrane in Single Molecule Tracking". Biophysical Journal. 88 (3): 2266–77. Bibcode:2005BpJ....88.2266R. doi:10.1529/biophysj.104.054106. PMC   1305276 . PMID   15613635.
  63. ↑ Chiantia, Salvatore; et al. (2006). "Effects of ceramide on liquid-ordered domains investigated by simultaneous AFM and FCS". Biophysical Journal. 90 (12): 4500–4508. Bibcode:2006BpJ....90.4500C. doi:10.1529/biophysj.106.081026. PMC   1471841 . PMID   16565041.
  64. ↑ Galvanetto, Nicola (2018). "Single-cell unroofing: probing topology and nanomechanics of native membranes". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1860 (12): 2532–2538. arXiv: 1810.01643 . Bibcode:2018arXiv181001643G. doi:10.1016/j.bbamem.2018.09.019. PMID   30273580. S2CID   52897823.
  65. ↑ Eggeling, Christian; Ringemann, Christian; Medda, Rebecca; Schwarzmann, Günter; Sandhoff, Konrad; Polyakova, Svetlana; Belov, Vladimir N.; Hein, Birka; et al. (2009). "Direct observation of the nanoscale dynamics of membrane lipids in a living cell". Nature. 457 (7233): 1159–62. Bibcode:2009Natur.457.1159E. doi:10.1038/nature07596. hdl: 11858/00-001M-0000-0012-D8CA-4 . PMID   19098897. S2CID   4428863.
  66. ↑ Thomas, S.; Kumar, R.S.; Casares, S.; Brumeanu, T.-D. (2003). "Sensitive detection of GM1 lipid rafts and TCR partitioning in the T cell membrane". Journal of Immunological Methods. 275 (1–2): 161–8. doi:10.1016/S0022-1759(03)00014-0. PMID   12667680.
  67. ↑ Thomas, Sunil; Kumar, Rajeev; Preda-Pais, Anca; Casares, Sofia; Brumeanu, Teodor-D. (2003). "A Model for Antigen-Specific T-Cell Anergy: Displacement of CD4-p56lck Signalosome from the Lipid Rafts by a Soluble, Dimeric Peptide-MHC Class II Chimera1". The Journal of Immunology. 170 (12): 5981–92. doi: 10.4049/jimmunol.170.12.5981 . PMID   12794125.
  68. ↑ Munro, Sean (2003). "Lipid rafts: elusive or illusive?". Cell. 115 (4): 377–88. doi: 10.1016/S0092-8674(03)00882-1 . PMID   14622593.
  69. ↑ Barenholz, Yechezkel (2004). "Sphingomyelin and Cholesterol: From Membrane Biophysics and Rafts to Potential Medical Applications". In Quinn, Peter J. (ed.). Membrane Dynamics and Domains. Subcellular Biochemistry. Vol. 37. pp. 167–215. doi:10.1007/978-1-4757-5806-1_5. ISBN   978-1-4419-3447-5. PMID   15376621.
  70. ↑ Pike, L. J.; Miller, JM (1998). "Cholesterol Depletion Delocalizes Phosphatidylinositol Bisphosphate and Inhibits Hormone-stimulated Phosphatidylinositol Turnover". Journal of Biological Chemistry. 273 (35): 22298–304. doi: 10.1074/jbc.273.35.22298 . PMID   9712847.
  71. ↑ Caroni, P. (2001). "NEW EMBO MEMBERS' REVIEW: Actin cytoskeleton regulation through modulation of PI(4,5)P2 rafts". The EMBO Journal. 20 (16): 4332–6. doi:10.1093/emboj/20.16.4332. PMC   125564 . PMID   11500359.
  72. ↑ Kwik, Jeanne; Boyle, Sarah; Fooksman, David; Margolis, Leonid; Sheetz, Michael P.; Edidin, Michael (2003). "Membrane cholesterol, lateral mobility, and the phosphatidylinositol 4,5-bisphosphate-dependent organization of cell actin". Proceedings of the National Academy of Sciences. 100 (24): 13964–9. Bibcode:2003PNAS..10013964K. doi: 10.1073/pnas.2336102100 . JSTOR   3148895. PMC   283529 . PMID   14612561.
  73. ↑ Edidin, Michael (2003). "THE STATE OF LIPID RAFTS: From Model Membranes to Cells". Annual Review of Biophysics and Biomolecular Structure. 32: 257–83. doi:10.1146/annurev.biophys.32.110601.142439. PMID   12543707. S2CID   13122250.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.