Related Research Articles
Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, and movement of new receptors to the cell membrane. The presence of integrins allows rapid and flexible responses to events at the cell surface.
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.
Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each other and to their surroundings. CAMs are crucial components in maintaining tissue structure and function. In fully developed animals, these molecules play an integral role in generating force and movement and consequently ensuring that organs are able to execute their functions normally. In addition to serving as "molecular glue", CAMs play important roles in the cellular mechanisms of growth, contact inhibition, and apoptosis. Aberrant expression of CAMs may result in a wide range of pathologies, ranging from frostbite to cancer.
Cell junctions or junctional complexes, are a class of cellular structures consisting of multiprotein complexes that provide contact or adhesion between neighboring cells or between a cell and the extracellular matrix in animals. They also maintain the paracellular barrier of epithelia and control paracellular transport. Cell junctions are especially abundant in epithelial tissues. Combined with cell adhesion molecules and extracellular matrix, cell junctions help hold animal cells together.
In cell biology, focal adhesions are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell. More precisely, focal adhesions are the sub-cellular structures that mediate the regulatory effects of a cell in response to ECM adhesion.
Protein subcellular localization prediction involves the prediction of where a protein resides in a cell, its subcellular localization.
In cellular biology, mechanotransduction is any of various mechanisms by which cells convert mechanical stimulus into electrochemical activity. This form of sensory transduction is responsible for a number of senses and physiological processes in the body, including proprioception, touch, balance, and hearing. The basic mechanism of mechanotransduction involves converting mechanical signals into electrical or chemical signals.
Biological crosstalk refers to instances in which one or more components of one signal transduction pathway affects another. This can be achieved through a number of ways with the most common form being crosstalk between proteins of signaling cascades. In these signal transduction pathways, there are often shared components that can interact with either pathway. A more complex instance of crosstalk can be observed with transmembrane crosstalk between the extracellular matrix (ECM) and the cytoskeleton.
In biology, juxtacrine signalling is a type of cell–cell or cell–extracellular matrix signalling in multicellular organisms that requires close contact. In this type of signalling, a ligand on one surface binds to a receptor on another adjacent surface. Hence, this stands in contrast to releasing a signaling molecule by diffusion into extracellular space, the use of long-range conduits like membrane nanotubes and cytonemes or the use of extracellular vesicles like exosomes or microvesicles. There are three types of juxtacrine signaling:
- A membrane ligand and a membrane protein of two adjacent cells interact.
- A communicating junction links the intracellular compartments of two adjacent cells, allowing transit of relatively small molecules.
- An extracellular matrix glycoprotein and a membrane protein interact.
CTGF, also known as CCN2 or connective tissue growth factor, is a matricellular protein of the CCN family of extracellular matrix-associated heparin-binding proteins. CTGF has important roles in many biological processes, including cell adhesion, migration, proliferation, angiogenesis, skeletal development, and tissue wound repair, and is critically involved in fibrotic disease and several forms of cancers.
Integrin-linked kinase is an enzyme that in humans is encoded by the ILK gene involved with integrin-mediated signal transduction. Mutations in ILK are associated with cardiomyopathies. It is a 59kDa protein originally identified in a yeast-two hybrid screen with integrin β1 as the bait protein. Since its discovery, ILK has been associated with multiple cellular functions including cell migration, proliferation, and adhesion.
Galectins are a class of proteins that bind specifically to β-galactoside sugars, such as N-acetyllactosamine, which can be bound to proteins by either N-linked or O-linked glycosylation. They are also termed S-type lectins due to their dependency on disulphide bonds for stability and carbohydrate binding. There have been about 15 galectins discovered in mammals, encoded by the LGALS genes, which are numbered in a consecutive manner. Only galectin-1, -2, -3, -4, -7, -7B, -8, -9, -9B, 9C, -10, -12, -13, -14, and -16 have been identified in humans. Galectin-5 and -6 are found in rodents, whereas galectin-11 and -15 are uniquely found in sheep and goats. Members of the galectin family have also been discovered in other mammals, birds, amphibians, fish, nematodes, sponges, and some fungi. Unlike the majority of lectins they are not membrane bound, but soluble proteins with both intra- and extracellular functions. They have distinct but overlapping distributions but found primarily in the cytosol, nucleus, extracellular matrix or in circulation. Although many galectins must be secreted, they do not have a typical signal peptide required for classical secretion. The mechanism and reason for this non-classical secretion pathway is unknown.
Talin is a high-molecular-weight cytoskeletal protein concentrated at regions of cell–substratum contact and, in lymphocytes, at cell–cell contacts. Discovered in 1983 by Keith Burridge and colleagues, talin is a ubiquitous cytosolic protein that is found in high concentrations in focal adhesions. It is capable of linking integrins to the actin cytoskeleton either directly or indirectly by interacting with vinculin and α-actinin.
PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes. It has been shown that when FAK was blocked, breast cancer cells became less metastatic due to decreased mobility.
Integrin alpha-V is a protein that in humans is encoded by the ITGAV gene.
Intercellular adhesion molecule 3 (ICAM3) also known as CD50, is a protein that in humans is encoded by the ICAM3 gene. The protein is constitutively expressed on the surface of leukocytes, which are also called white blood cells and are part of the immune system. ICAM3 mediates adhesion between cells by binding to specific integrin receptors. It plays an important role in the immune cell response through its facilitation of interactions between T cells and dendritic cells, which allows for T cell activation. ICAM3 also mediates the clearance of cells undergoing apoptosis by attracting and binding macrophages, a type of cell that breaks down infected or dying cells through a process known as phagocytosis, to apoptotic cells.
Fermitin family homolog 3) (FERMT3), also known as kindlin-3 (KIND3), MIG2-like protein (MIG2B), or unc-112-related protein 2 (URP2) is a protein that in humans is encoded by the FERMT3 gene. The kindlin family of proteins, member of the B4.1 superfamily, comprises three conserved protein homologues, kindlin 1, 2, and 3. They each contain a bipartite FERM domain comprising four subdomains F0, F1, F2, and F3 that show homology with the FERM head (H) domain of the cytoskeletal Talin protein. Kindlins have been linked to Kindler syndrome, leukocyte adhesion deficiency, cancer and other acquired human diseases. They are essential in the organisation of focal adhesions that mediate cell-extracellular matrix junctions and are involved in other cellular compartments that control cell-cell contacts and nucleus functioning. Therefore, they are responsible for cell to cell crosstalk via cell-cell contacts and integrin mediated cell adhesion through focal adhesion proteins and as specialised adhesion structures of hematopoietic cells they are also present in podosome's F actin surrounding ring structure. Isoform 2 may act as a repressor of NF-kappa-B and apoptosis
Secretomics is a type of proteomics which involves the analysis of the secretome—all the secreted proteins of a cell, tissue or organism. Secreted proteins are involved in a variety of physiological processes, including cell signaling and matrix remodeling, but are also integral to invasion and metastasis of malignant cells. Secretomics has thus been especially important in the discovery of biomarkers for cancer and understanding molecular basis of pathogenesis. The analysis of the insoluble fraction of the secretome has been termed matrisomics.
SNED1 is an extracellular matrix (ECM) protein expressed at low levels in a wide range of tissues. The gene encoding SNED1 is located in the human chromosome 2 at locus q37.3. The corresponding mRNA isolated from the spleen and is 6834bp in length, and the corresponding protein is 1413 amino-acid long. The mouse ortholog of SNED1 was cloned in 2004 from the embryonic kidney by Leimester et al. SNED1 present domains characteristic of ECM proteins, including an amino-terminal NIDO domain, several calcium binding EGF-like domains (EGF_CA), a Sushi domain also known as complement control protein (CCP) domain, and three type III fibronectin (FN3) domains in the carboxy-terminal region.
The term Adhesome was first used by Richard Hynes to describe the complement of cell-cell and cell-matrix adhesion receptors in an organism and later expanded by Benny Geiger and co-workers to include the entire network of structural and signaling proteins involved in regulating cell-matrix adhesion.
References
- ↑ Tjalsma, H.; Antelmann, H.; Jongbloed, J. D.H.; Braun, P. G.; Darmon, E.; Dorenbos, R.; Dubois, J.-Y. F.; Westers, H.; Zanen, G.; Quax, W. J.; Kuipers, O. P.; Bron, S.; Hecker, M.; van Dijl, J. M. (8 June 2004). "Proteomics of Protein Secretion by Bacillus subtilis: Separating the "Secrets" of the Secretome". Microbiology and Molecular Biology Reviews. 68 (2): 207–233. doi: 10.1128/MMBR.68.2.207-233.2004 . PMC 419921 . PMID 15187182.
- 1 2 Agrawal GK, Jwa NS, Lebrun MH, Job D, Rakwal R (February 2010). "Plant secretome: unlocking secrets of the secreted proteins". Proteomics. 10 (4): 799–827. doi:10.1002/pmic.200900514. PMID 19953550. S2CID 20647387.
- ↑ Hynes, R. O.; Naba, A. (21 September 2011). "Overview of the Matrisome--An Inventory of Extracellular Matrix Constituents and Functions". Cold Spring Harbor Perspectives in Biology. 4 (1): a004903. doi:10.1101/cshperspect.a004903. PMC 3249625 . PMID 21937732.
- ↑ Ben-Shlomo, I.; Yu Hsu, S.; Rauch, R.; Kowalski, H. W.; Hsueh, A. J. W. (17 June 2003). "Signaling Receptome: A Genomic and Evolutionary Perspective of Plasma Membrane Receptors Involved in Signal Transduction". Science Signaling. 2003 (187): re9. doi:10.1126/stke.2003.187.re9. PMID 12815191. S2CID 12803444.
- ↑ Zaidel-Bar, Ronen; Itzkovitz, Shalev; Ma'ayan, Avi; Iyengar, Ravi; Geiger, Benjamin (August 2007). "Functional atlas of the integrin adhesome". Nature Cell Biology. 9 (8): 858–867. doi:10.1038/ncb0807-858. PMC 2735470 . PMID 17671451.
- ↑ Horton, Edward R.; Byron, Adam; Askari, Janet A.; Ng, Daniel H. J.; Millon-Frémillon, Angélique; Robertson, Joseph; Koper, Ewa J.; Paul, Nikki R.; Warwood, Stacey; Knight, David; Humphries, Jonathan D.; Humphries, Martin J. (19 October 2015). "Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly". Nature Cell Biology. 17 (12): 1577–1587. doi:10.1038/ncb3257. PMC 4663675 . PMID 26479319.
- ↑ Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, et al. (January 2015). "Proteomics. Tissue-based map of the human proteome". Science. 347 (6220): 1260419. doi:10.1126/science.1260419. PMID 25613900. S2CID 802377.
- ↑ Xu R, Greening DW, Zhu HJ, Takahashi N, Simpson RJ (April 2016). "Extracellular vesicle isolation and characterization: toward clinical application". The Journal of Clinical Investigation. 126 (4): 1152–62. doi:10.1172/JCI81129. PMC 4811150 . PMID 27035807.
- 1 2 Mukherjee P, Mani S (November 2013). "Methodologies to decipher the cell secretome". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1834 (11): 2226–32. doi:10.1016/j.bbapap.2013.01.022. PMC 3652893 . PMID 23376189.