Incell biology, avesicle is a structurewithin oroutside acell, consisting of liquid or cytoplasm enclosed by alipid bilayer. Vesicles form naturally during the processes of secretion (exocytosis), uptake (endocytosis), and the transport of materials within theplasma membrane. Alternatively, they may be prepared artificially, in which case they are calledliposomes (not to be confused withlysosomes). If there is only onephospholipid bilayer, the vesicles are calledunilamellar liposomes; otherwise they are calledmultilamellar liposomes.[1] The membrane enclosing the vesicle is also alamellar phase, similar to that of theplasma membrane, and intracellular vesicles can fuse with the plasma membrane to release their contents outside the cell. Vesicles can also fuse with otherorganelles within the cell. A vesicle released from the cell is known as anextracellular vesicle.
Vesicles perform a variety of functions. Because it is separated from thecytosol, the inside of the vesicle can be made to be different from the cytosolic environment. For this reason, vesicles are a basic tool used by the cell for organizing cellular substances. Vesicles are involved inmetabolism, transport, buoyancy control,[2] and temporary storage of food and enzymes. They can also act as chemical reaction chambers.
Closed structure formed by amphiphilic molecules that contains solvent (usually water).[3]
The 2013Nobel Prize in Physiology or Medicine was shared byJames Rothman,Randy Schekman andThomas Südhof for their roles in elucidating (building upon earlier research, some of it by their mentors) the makeup and function of cell vesicles, especially in yeasts and in humans, including information on each vesicle's parts and how they are assembled. Vesicle dysfunction is thought to contribute toAlzheimer's disease,diabetes, some hard-to-treat cases ofepilepsy, some cancers and immunological disorders and certain neurovascular conditions.[4][5]
Lysosomes are involved in cellular digestion. Food can be taken from outside the cell into food vacuoles by a process calledendocytosis. These food vacuoles fuse with lysosomes which break down the components so that they can be used in the cell. This form of cellular eating is calledphagocytosis.
Lysosomes are also used to destroy defective or damaged organelles in a process calledautophagy. They fuse with the membrane of the damaged organelle, digesting it.
Transport vesicles can move molecules between locations inside the cell, e.g., proteins from the roughendoplasmic reticulum to theGolgi apparatus.
Membrane-bound and secreted proteins are made onribosomes found in therough endoplasmic reticulum. Most of these proteins mature in theGolgi apparatus before going to their final destination which may be tolysosomes,peroxisomes, or outside of the cell. These proteins travel within the cell inside transport vesicles.
Secretory vesicles contain materials that are to be excreted from the cell. Cells have many reasons to excrete materials.One reason is to dispose of wastes.Another reason is tied to the function of the cell. Within a larger organism, some cells are specialized to produce certain chemicals. These chemicals are stored in secretory vesicles and released when needed.
In animals,endocrine tissues releasehormones into the bloodstream. These hormones are stored within secretory vesicles. A good example is an endocrine tissue found in theislets of Langerhans in thepancreas. Thistissue contains many cell types that are defined by which hormones they produce.
Bacteria,archaea, fungi and parasites release membrane vesicles (MVs) containing varied but specialized toxic compounds and biochemical signal molecules, which are transported to target cells to initiate processes in favour of the microbe, which include invasion of host cells and killing of competing microbes in the same niche.[6]
Extracellular vesicles (EVs) are lipid bilayer-delimited particles produced by all domains of life including complex eukaryotes, both Gram-negative and Gram-positive bacteria, mycobacteria, and fungi.[7][8]
Ectosomes/microvesicles are shed directly from the plasma membrane and can range in size from around 30nm to larger than a micron in diameter[9]: Table 1 ). These may include large particles such asapoptotic blebs released by dying cells,[10][9]: Table 1 large oncosomes released by some cancer cells, or "exophers," released by nematode neurons[11] and mouse cardiomyocytes.
Different types of EVs may be separated based on density[9]: Table 1 (by gradientdifferential centrifugation), size, or surface markers.[12] However, EV subtypes have an overlapping size and density ranges, and subtype-unique markers must be established on a cell-by-cell basis. Therefore, it is difficult to pinpoint the biogenesis pathway that gave rise to a particular EV after it has left the cell.[8]
In humans, endogenous extracellular vesicles likely play a role in coagulation, intercellular signaling and waste management.[9] They are also implicated in the pathophysiological processes involved in multiple diseases, including cancer.[13] Extracellular vesicles have raised interest as a potential source of biomarker discovery because of their role in intercellular communication, release into easily accessible body fluids and the resemblance of their molecular content to that of the releasing cells.[14] The extracellular vesicles of(mesenchymal) stem cells, also known as thesecretome of stem cells, are being researched and applied for therapeutic purposes, predominantlydegenerative,auto-immune and/orinflammatory diseases.[15]
In Gram-negative bacteria, EVs are produced by the pinching off of the outer membrane; however, how EVs escape the thick cell walls of Gram-positive bacteria, mycobacteria and fungi is still unknown. These EVs contain varied cargo, including nucleic acids, toxins, lipoproteins and enzymes and have important roles in microbial physiology and pathogenesis. In host–pathogen interactions, gram negative bacteria produce vesicles which play roles in establishing a colonization niche, carrying and transmitting virulence factors into host cells and modulating host defense and response.[16]
Oceancyanobacteria have been found to continuously release vesicles containing proteins, DNA and RNA into the open ocean. Vesicles carrying DNA from diverse bacteria are abundant in coastal and open-ocean seawater samples.[17]
TheRNA world hypothesis assumes that the firstself-replicatinggenomes were strands of RNA. This hypothesis contains the idea that RNA strands formedribozymes (folded RNA molecules) capable of catalyzing RNA replication. These primordial biological catalysis were considered to be contained within vesicles (protocells) with membranes composed offatty acids and relatedamphiphiles.[18] Template-directed RNA synthesis by the copying of RNA templates inside fatty acid vesicles has been demonstrated by Adamata and Szostak.[18]
Gas vesicles are used byarchaea,bacteria andplanktonic microorganisms, possibly to control vertical migration by regulating the gas content and therebybuoyancy, or possibly to position the cell for maximum solar light harvesting. These vesicles are typically lemon-shaped or cylindrical tubes made out of protein;[19] their diameter determines the strength of the vesicle with larger ones being weaker. The diameter of the vesicle also affects its volume and how efficiently it can provide buoyancy. In cyanobacteria, natural selection has worked to create vesicles that are at the maximum diameter possible while still being structurally stable. The protein skin is permeable to gases but not water, keeping the vesicles from flooding.[2]
Matrix vesicles are located within the extracellular space, or matrix. Usingelectron microscopy, they were discovered independently in 1967 by H. Clarke Anderson[20] and Ermanno Bonucci.[21] These cell-derived vesicles are specialized to initiatebiomineralisation of the matrix in a variety of tissues, includingbone,cartilage anddentin. During normalcalcification, a major influx of calcium and phosphate ions into the cells accompanies cellularapoptosis (genetically determined self-destruction) and matrix vesicle formation. Calcium-loading also leads to formation ofphosphatidylserine:calcium:phosphate complexes in the plasma membrane mediated in part by a protein calledannexins. Matrix vesicles bud from the plasma membrane at sites of interaction with the extracellular matrix. Thus, matrix vesicles convey to the extracellular matrix calcium, phosphate, lipids and the annexins which act to nucleate mineral formation. These processes are precisely coordinated to bring about, at the proper place and time, mineralization of the tissue's matrix unless the Golgi are non-existent.[citation needed]
Multivesicular body, or MVB, is a membrane-bound vesicle containing a number of smaller vesicles.[22]
Some vesicles are made when part of the membrane pinches off the endoplasmic reticulum or the Golgi complex. Others are made when an object outside of the cell is surrounded by the cell membrane.[citation needed]
The vesicle "coat" is a collection of proteins that serve to shape the curvature of a donor membrane, forming the rounded vesicle shape. Coat proteins can also function to bind to various transmembrane receptor proteins, called cargo receptors. These receptors help select what material is endocytosed inreceptor-mediated endocytosis or intracellular transport.
There are three types of vesicle coats:clathrin,COPI andCOPII. The various types of coat proteins help with sorting of vesicles to their final destination. Clathrin coats are found on vesicles trafficking between theGolgi andplasma membrane, the Golgi andendosomes and the plasma membrane and endosomes. COPI coated vesicles are responsible for retrograde transport from the Golgi to the ER, while COPII coated vesicles are responsible for anterograde transport from the ER to the Golgi.
Theclathrin coat is thought to assemble in response to regulatoryG protein. A protein coat assembles and disassembles due to anADP ribosylation factor (ARF) protein.
Surface proteins calledSNAREs identify the vesicle's cargo and complementary SNAREs on the target membrane act to cause fusion of the vesicle and target membrane. Such v-SNARES are hypothesised to exist on the vesicle membrane, while the complementary ones on the target membrane are known as t-SNAREs.[citation needed]
Often SNAREs associated with vesicles or target membranes are instead classified as Qa, Qb, Qc, or R SNAREs owing to further variation than simply v- or t-SNAREs. An array of different SNARE complexes can be seen in different tissues and subcellular compartments, with 38 isoforms currently identified in humans.[23]RegulatoryRab proteins are thought to inspect the joining of the SNAREs. Rab protein is a regulatory GTP-binding protein and controls the binding of these complementary SNAREs for a long enough time for the Rab protein to hydrolyse its bound GTP and lock the vesicle onto the membrane.
SNAREs proteins in plants are understudied compared to fungi and animals. The cell botanistNatasha Raikhel has done some of the basic research in this area, including Zheng et al 1999 in which she and her team foundAtVTI1a to be essential toGolgi⇄vacuole transport.[24]
Vesicle fusion can occur in one of two ways: full fusion orkiss-and-run fusion. Fusion requires the two membranes to be brought within 1.5 nm of each other. For this to occur water must be displaced from the surface of the vesicle membrane. This is energetically unfavorable and evidence suggests that the process requiresATP,GTP andacetyl-coA. Fusion is also linked to budding, which is why the term budding and fusing arises.
Membrane proteins serving asreceptors are sometimes tagged fordownregulation by the attachment ofubiquitin. After arriving anendosome via the pathway described above, vesicles begin to form inside the endosome, taking with them the membrane proteins meant for degradation; When the endosome either matures to become alysosome or is united with one, the vesicles are completely degraded.Without this mechanism, only the extracellular part of the membrane proteins would reach the lumen of thelysosome and only this part would be degraded.[25]
It is because of these vesicles that the endosome is sometimes known as amultivesicular body. The pathway to their formation is not completely understood; unlike the other vesicles described above, the outer surface of the vesicles is not in contact with thecytosol.
Producing membrane vesicles is one of the methods to investigate various membranes of the cell. After the living tissue is crushed intosuspension, various membranes form tiny closed bubbles. Big fragments of the crushed cells can be discarded by low-speed centrifugation and later the fraction of the known origin (plasmalemma,tonoplast, etc.) can be isolated by precise high-speed centrifugation in the density gradient. Usingosmotic shock, it is possible temporarily open vesicles (filling them with the required solution) and then centrifugate down again and resuspend in a different solution. Applying ionophores likevalinomycin can create electrochemical gradients comparable to the gradients inside living cells.
Vesicles are mainly used in two types of research:
To find and later isolate membrane receptors that specifically bind hormones and various other important substances.[26]
To investigate transport of various ions or other substances across the membrane of the given type.[27] While transport can be more easily investigated withpatch clamp techniques, vesicles can also be isolated from objects for which a patch clamp is not applicable.
Artificial vesicles are classified into three groups based on their size: small unilamellar liposomes/vesicles (SUVs) with a size range of 20–100 nm, large unilamellar liposomes/vesicles (LUVs) with a size range of 100–1000 nm and giant unilamellar liposomes/vesicles (GUVs) with a size range of 1–200 μm.[28] Smaller vesicles in the same size range as trafficking vesicles found in living cells are frequently used inbiochemistry and related fields. For such studies, a homogeneous phospholipid vesicle suspension can be prepared by extrusion orsonication,[29] or by rapid injection of a phospholipid solution into an aqueous buffer solution.[30] In this way, aqueous vesicle solutions can be prepared of different phospholipid composition, as well as different sizes of vesicles. Larger synthetically made vesicles such as GUVs are used for in vitro studies incell biology in order to mimic cell membranes. These vesicles are large enough to be studied using traditional fluorescence light microscopy. A variety of methods exist to encapsulate biological reactants like protein solutions within such vesicles, making GUVs an ideal system for the in vitro recreation (and investigation) of cell functions in cell-like model membrane environments.[31] These methods include microfluidic methods, which allow for a high-yield production of vesicles with consistent sizes.[32]
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^Batzri S, Korn ED (April 1973). "Single bilayer liposomes prepared without sonication".Biochimica et Biophysica Acta (BBA) - Biomembranes.298 (4):1015–9.doi:10.1016/0005-2736(73)90408-2.PMID4738145.