ExoCarta

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ExoCarta
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Content
DescriptionExosomal proteins, RNA and lipids database
Contact
Research center La Trobe Institute for Molecular Science
Authors Suresh Mathivanan
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Website http://www.exocarta.org

ExoCarta is a manually curated database of exosomal proteins, RNA and lipids. [1] [2]

Contents

Exosomes are cell-derived vesicles that are present in many and perhaps all biological fluids, including blood, urine, and cultured medium of cell cultures. [3] [4] The reported diameter of exosomes is between 30 and 100 nm, which is larger than LDL, but much smaller than for example, red blood cells. Exosomes are either released from the cell when multivesicular bodies fuse with the plasma membrane or they are released directly from the plasma membrane. [5] It is becoming increasingly clear that exosomes have specialized functions and play a key role in, for example, coagulation, intercellular signaling, and waste management. [3] Consequently, there is a growing interest in the clinical applications of exosomes. Exosomes can potentially be used for prognosis, therapy, and biomarkers for health and disease.

Bioinformatics analysis of exosomes

Exosomes contain RNA, proteins, lipids and metabolites that is reflective of the cell type of origin. As exosomes contain numerous bioactive molecules, including proteins, nucleic acids, lipids, sugars, and related conjugates, large scale analysis including proteomics and transcriptomics is often performed. [6] Currently, to analyse these data, non-commercial tools such as FunRich [7] can be used to identify over-represented groups of molecules.

Related Research Articles

Biological membrane Enclosing or separating membrane in organisms acting as selective semi-permeable barrier

A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates cell from the external environment or creates intracellular compartments. Biological membranes, in the form of eukaryotic cell membranes, consist of a phospholipid bilayer with embedded, integral and peripheral proteins used in communication and transportation of chemicals and ions. The bulk of lipid in a cell membrane provides a fluid matrix for proteins to rotate and laterally diffuse for physiological functioning. Proteins are adapted to high membrane fluidity environment of lipid bilayer with the presence of an annular lipid shell, consisting of lipid molecules bound tightly to surface of integral membrane proteins. The cell membranes are different from the isolating tissues formed by layers of cells, such as mucous membranes, basement membranes, and serous membranes.

Endomembrane system Membranes in the cytoplasm of a eukaryotic cell

The endomembrane system is composed of the different membranes that are suspended in the cytoplasm within a eukaryotic cell. These membranes divide the cell into functional and structural compartments, or organelles. In eukaryotes the organelles of the endomembrane system include: the nuclear membrane, the endoplasmic reticulum, the Golgi apparatus, lysosomes, vesicles, endosomes, and plasma (cell) membrane among others. The system is defined more accurately as the set of membranes that form a single functional and developmental unit, either being connected directly, or exchanging material through vesicle transport. Importantly, the endomembrane system does not include the membranes of plastids or mitochondria, but might have evolved partially and from the actions of the latter.

Endocytosis 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.

Vesicle (biology and chemistry) Any small, fluid-filled, spherical organelle enclosed by a membrane

In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form naturally during the processes of secretion (exocytosis), uptake (endocytosis) and transport of materials within the plasma membrane. Alternatively, they may be prepared artificially, in which case they are called liposomes. If there is only one phospholipid bilayer, they are called unilamellar liposome vesicles; otherwise they are called multilamellar. The membrane enclosing the vesicle is also a lamellar phase, similar to that of the plasma membrane, and intracellular vesicles can fuse with the plasma membrane to release their contents outside the cell. Vesicles can also fuse with other organelles within the cell. A vesicle released from the cell is known as an extracellular vesicle.

Exocytosis Active transport and bulk transport in which a cell transports molecules out of the cell

Exocytosis is a form of active transport and bulk transport in which a cell transports molecules out of the cell. As an active transport mechanism, exocytosis requires the use of energy to transport material. Exocytosis and its counterpart, endocytosis, are used by all cells because most chemical substances important to them are large polar molecules that cannot pass through the hydrophobic portion of the cell membrane by passive means. Exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. Exocytosis occurs via secretory portals at the cell plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structure at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell.

Lipid bilayer A thin polar membrane made of two layers of lipid molecules

The lipid bilayer is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many viruses are made of a lipid bilayer, as are the nuclear membrane surrounding the cell nucleus, and membranes of the membrane-bound organelles in the cell. The lipid bilayer is the barrier that keeps ions, proteins and other molecules where they are needed and prevents them from diffusing into areas where they should not be. Lipid bilayers are ideally suited to this role, even though they are only a few nanometers in width, because they are impermeable to most water-soluble (hydrophilic) molecules. Bilayers are particularly impermeable to ions, which allows cells to regulate salt concentrations and pH by transporting ions across their membranes using proteins called ion pumps.

Fluid mosaic model Describe the fluid mosaic model of plasma membrane

The fluid mosaic model explains various observations regarding the structure of functional cell membranes. According to this biological model, there is a lipid bilayer in which protein molecules are embedded. The lipid bilayer gives fluidity and elasticity to the membrane. Small amounts of carbohydrates are also found in the cell membrane. The biological model, which was devised by SJ Singer and G. L. Nicolson in 1972, describes the cell membrane as a two-dimensional liquid that restricts the lateral diffusion of membrane components. Such domains are defined by the existence of regions within the membrane with special lipid and protein cocoon that promote the formation of lipid rafts or protein and glycoprotein complexes. Another way to define membrane domains is the association of the lipid membrane with the cytoskeleton filaments and the extracellular matrix through membrane proteins. The current model describes important features relevant to many cellular processes, including: cell-cell signaling, apoptosis, cell division, membrane budding, and cell fusion. The fluid mosaic model is the most acceptable model of the plasma membrane. Its main function is to separate the contents of the cell from the exterior.

Endosome Vacuole to which materials ingested by endocytosis are delivered

Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are part 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.

Synaptic vesicle Neurotransmitters that are released at the synapse

In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell. The area in the axon that holds groups of vesicles is an axon terminal or "terminal bouton". Up to 130 vesicles can be released per bouton over a ten-minute period of stimulation at 0.2 Hz. In the visual cortex of the human brain, synaptic vesicles have an average diameter of 39.5 nanometers (nm) with a standard deviation of 5.1 nm.

The bacterium, despite its simplicity, contains a well-developed cell structure which is responsible for some of its unique biological structures and pathogenicity. Many structural features are unique to bacteria and are not found among archaea or eukaryotes. Because of the simplicity of bacteria relative to larger organisms and the ease with which they can be manipulated experimentally, the cell structure of bacteria has been well studied, revealing many biochemical principles that have been subsequently applied to other organisms.

Extracellular space refers to the part of a multicellular organism outside the cells, usually taken to be outside the plasma membranes, and occupied by fluid.

Exosome (vesicle) Membrane-bound extracellular vesicles

Exosomes are membrane-bound extracellular vesicles (EVs) that are produced in the endosomal compartment of most eukaryotic cells. The multivesicular body (MVB) is an endosome defined by intraluminal vesicles (ILVs) that bud inward into the endosomal lumen. If the MVB fuses with the cell surface, these ILVs are released as exosomes.

Microvesicles Type of extracellular vesicle

Microvesicles are a type of extracellular vesicle (EV) that are released from the cell membrane. In multicellular organisms, microvesicles and other EVs are found both in tissues and in many types of body fluids. Delimited by a phospholipid bilayer, microvesicles can be as small as the smallest EVs or as large as 1000 nm. They are considered to be larger, on average, than intracellularly-generated EVs known as exosomes. Microvesicles play a role in intercellular communication and can transport molecules such as mRNA, miRNA, and proteins between cells.

Prostasomes are extracellular vesicles secreted by the prostate gland epithelial cells into seminal fluid. They possess an unusual lipid composition and a tight and highly ordered structure of their lipid bilayer membrane, resembling that of lipid raft domains. Prostasomes appear to improve sperm motility and protect against attacks from the female immune defense during the passage to the egg.

ADAM7

Disintegrin and metalloproteinase domain-containing protein 7 is a protein that in humans is encoded by the ADAM7 gene. ADAM7 is an 85-kDa enzyme that is a member of the transmembrane ADAM protein family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. ADAM7 is important for the maturation of sperm cells in mammals. ADAM7 is also denoted as: ADAM_7, ADAM-7, EAPI, GP-83, and GP83.

Cell membrane Biological membrane that separates the interior of a cell from its outside environment

The cell membrane is a biological membrane that separates the interior of all cells from the outside environment and protects the cell from its environment. The cell membrane consists of a lipid bilayer, made up of two layers of phospholipids with cholesterols interspersed between them, maintaining appropriate membrane fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that span the membrane and serve as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes to facilitate interaction with the cell's environment. Glycolipids embedded in the outer lipid layer serve a similar purpose. The cell membrane controls the movement of substances in and out of cells and organelles, being selectively permeable to ions and organic molecules. In addition, cell membranes are involved in a variety of cellular processes such as cell adhesion, ion conductivity and cell signalling and serve as the attachment surface for several extracellular structures, including the cell wall and the carbohydrate layer called the glycocalyx, as well as the intracellular network of protein fibers called the cytoskeleton. In the field of synthetic biology, cell membranes can be artificially reassembled.

Extracellular RNA (exRNA) describes RNA species present outside of the cells in which they were transcribed. Carried within extracellular vesicles, lipoproteins, and protein complexes, exRNAs are protected from ubiquitous RNA-degrading enzymes. exRNAs may be found in the environment or, in multicellular organisms, within the tissues or biological fluids such as venous blood, saliva, breast milk, urine, semen, menstrual blood, and vaginal fluid. Although their biological function is not fully understood, exRNAs have been proposed to play a role in a variety of biological processes including syntrophy, intercellular communication, and cell regulation. The United States National Institutes of Health (NIH) published in 2012 a set of Requests for Applications (RFAs) for investigating extracellular RNA biology. Funded by the NIH Common Fund, the resulting program was collectively known as the Extracellular RNA Communication Consortium (ERCC). The ERCC was renewed for a second phase in 2019.

The secretome is the set of proteins expressed by an organism and secreted into the extracellular space. In humans, this subset of the proteome encompasses 13-20% of all proteins, including cytokines, growth factors, extracellular matrix proteins and regulators, and shed receptors. The secretome of a specific tissue can be measured by mass spectrometry and its analysis constitutes a type of proteomics known as secretomics.

Extracellular vesicles (EVs) are lipid bilayer-delimited particles that are naturally released from almost all types of cell and, unlike a cell, cannot replicate. EVs range in diameter from near the size of the smallest physically possible unilamellar liposome to as large as 10 microns or more, although the vast majority of EVs are smaller than 200 nm. EVs can be divided according to size and synthesis route into Exosomes, microvesicles and apoptotic bodies. They carry a cargo of proteins, nucleic acids, lipids, metabolites, and even organelles from the parent cell. Most cells that have been studied to date are thought to release EVs, including some archaeal, bacterial, fungal, and plant cells that are surrounded by cell walls. A wide variety of EV subtypes have been proposed, defined variously by size, biogenesis pathway, cargo, cellular source, and function, leading to a historically heterogenous nomenclature including terms like exosomes and ectosomes.

The Journal of Extracellular Vesicles is a peer-reviewed open-access scientific journal covering research on lipid bilayer-delimited particles known as extracellular vesicles (EVs). EVs are released from cells and include endosome-origin exosomes and plasma membrane-derived ectosomes/microvesicles. The journal is helmed by Editor-in-Chief Jan Lötvall and is published by Wiley on behalf of the International Society for Extracellular Vesicles (ISEV). It was established in 2012. Until August 2019, the editors-in-chief were Clotilde Théry, Yong Song Gho, and Peter Quesenberry. They were succeeded by Jan Lötvall.

References

  1. Mathivanan, Suresh; Fahner Cassie J; Reid Gavin E; Simpson Richard J (Oct 2011). "ExoCarta 2012: database of exosomal proteins, RNA and lipids". Nucleic Acids Research. 40 (Database issue): D1241–4. doi:10.1093/nar/gkr828. PMC   3245025 . PMID   21989406.
  2. Mathivanan S, Simpson RJ (2009). "ExoCarta: A compendium of exosomal proteins and RNA". Proteomics. 9 (21): 4997–5000. doi:10.1002/pmic.200900351. PMID   19810033. S2CID   22275212.
  3. 1 2 van der Pol E; Böing, AN; Harrison P; Sturk A; Nieuwland R (2012). "Classification, functions, and clinical relevance of extracellular vesicles". Pharmacol. Rev. 64 (3): 676–705. doi:10.1124/pr.112.005983. PMID   22722893. S2CID   7764903.
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  6. Rudraprasad, Dhanwini; Rawat, Aadish; Joseph, Joveeta (2022-01-01). "Exosomes, extracellular vesicles and the eye". Experimental Eye Research. 214: 108892. doi:10.1016/j.exer.2021.108892. ISSN   0014-4835. PMID   34896308. S2CID   245028439.
  7. Pathan, M; Keerthikumar, S; Ang, C. S.; Gangoda, L; Quek, C. Y.; Williamson, N. A.; Mouradov, D; Sieber, O. M.; Simpson, R. J.; Salim, A; Bacic, A; Hill, A; Stroud, D. A.; Ryan, M. T.; Agbinya, J. I.; Mariadasson, J. M.; Burgess, A. W.; Mathivanan, S (2015). "Technical brief funrich: An open access standalone functional enrichment and interaction network analysis tool". Proteomics. 15 (15): 2597–601. doi:10.1002/pmic.201400515. PMID   25921073. S2CID   28583044.