SNARE proteins are the key components of the molecular machinery that drives fusion of membranes in exocytosis. Their function however is subject to fine tuning by various regulatory protein collectively referred to as SNARE masters.
Tags: Integral membrane proteins, Membrane proteins, Proteins
Synaptobrevins (synaptobrevin isotypes 1-2) are small integral membrane proteins of secretory vesicles with molecular weight of 18 kilodalton (kDa) that are part of the vesicle-associated membrane protein (VAMP) family.[1][2][3][4][5] Synaptobrevin is one of the SNARE proteins involved in formation of the SNARE complexes.
Synaptobrevin is degraded by Tetanospasmin, a protein derived from Clostridium tetani.
Out of four ?-helices of the core SNARE complex one is contributed by synaptobrevin, one by syntaxin, and two by SNAP-25 (in neurons).
Because all proteins belonging to VAMP/synaptobrevin family share common structural feature, they have been classified as R-SNAREs. An alternative classification (v- and t-SNAREs) exists that takes into account origin of synaptobrevin-bearing organelle rather than their structural properties.
SNAREs are small, abundant and mostly plasma membrane-bound proteins. Although they vary considerably in structure and size, all share a segment in their cytosolic domain called a SNARE motif that consists of 60-70 amino acids that are capable of reversible assembly into tight, four-helix bundles called "trans"-SNARE complexes. The readily-formed metastable "trans" complexes are composed of three SNAREs: syntaxin 1 and SNAP-25 resident in cell membrane and synaptobrevin (also referred to as vesicle-associated membrane protein or VAMP) anchored in the vesicular membrane. In neuronal exocytosis syntaxin and synaptobrevin are anchored in respective membranes by their C-terminal domains, whereas SNAP-25 is tethered to
Synaptophysin, also known as SYP, is a human gene.[1] The protein encoded by this gene is a synaptic vesicle glycoprotein with four transmembrane domains weighing 38kDa. It is present in neuroendocrine cells and in virtually all neurons in the brain and spinal cord that participate in synaptic transmission. It acts as a marker for neuroendocrine tumors. The gene for this protein is located on the X chromosome (Xp11.23-p11.22). The exact function of the protein is unknown: it interacts with the essential synaptic vesicle protein synaptobrevin, but when the synaptophysin gene is experimentally inactivated in animals, they still develop and function normally[2].
Assembly of the SNAREs into the "trans" complexes likely bridges the opposing lipid bilayers of membranes belonging to cell and secretory granule, bringing them in proximity and inducing their fusion. The influx of calcium into the cell triggers the completion of the assembly reaction, which is mediated by an interaction between the putative calcium sensor, synaptotagmin, with membrane lipids and/or the partially assembled SNARE complex. According to the "zipper" hypothesis, the complex assembly starts at the N-terminal parts of SNARE motifs and proceeds towards the C-termini that anchor interacting proteins in membranes. Formation of the "trans"-SNARE complex proceeds through an intermediate
R-SNAREs are proteins that contribute an arginine (R) residue in the formation of the zero ionic layer in the assembled core SNARE complex. One particular R-SNARE is synaptobrevin, which is located in the synaptic vesicles. Q-SNAREs are proteins that contribute a glutamine (Q) residue in the formation of the zero ionic layer in the assembled core SNARE complex. Q-SNAREs are syntaxin and SNAP-25. The core SNARE complex is a 4-?-helix bundle.[2] Synaptobrevin and syntaxin contribute one ?-helix each, while SNAP-25 participates with two ?-helices (abbreviated as Sn1 and Sn2). The interacting amino acid residues that zip the SNARE complex can be grouped
The main function of crystallins at least in the lens of the eye is probably to increase the refractive index while not obstructing light. However, this is not their only function. It is becoming increasingly clear that crystallins may have a several metabolic and regulatory functions, both within the lens and in other parts of the body [5].
Syntaxins possess a single C-terminal transmembrane domain, a SNARE domain (known as H3), and an N-terminal regulatory domain (Habc). The SNARE (H3) domain binds to both synaptobrevin and SNAP-25 forming the core SNARE complex. Formation of this incredibly stable SNARE core complex is believed to generate the free energy required to initiate fusion between the vesicle membrane and plasma membrane. The N-terminal Habc domain is formed by 3 ?-helices and when collapsed onto its own H3 helix forms an inactive "closed" syntaxin conformation. This closed conformation of syntaxin is believed to be stabilized by binding of nSec1 (Munc18), although more recent data
The protein has no known natural ligand[2] and its function is unclear. It is suspected that it acts as a calcium channel in the cell membran
SAP97 is expressed throughout the body in epithelial cells, including the kidney and brain[1]. There is some evidence that SAP97 regulates cell-to-cell adhesion during cell death, and may interact with HPV. In the brain, SAP97's function is involved in the trafficking of transmembrane receptors from the ER to the plasma membrane[2]. SAP97's function has been investigated by reducing its expression by knockout or increasing its expression heterologously. Mice in which the SAP97 gene has been knocked out die perinatally, have a cleft palate, and deficiencies in renal function.[3][4] Overexpression of SAP97 in mammalian neurons leads to increased synaptic strength. [5]
ER-? may have anti-proliferative effects and therefore oppose the actions of ER-? in reproductive tissue.[4] ER-? may also have an important role in adpative function of the lung during pregnancy.[5]
There is a vast array of studies investingating the function of "membrane channels", these frequently combine the patch clamp technique with pharmacology. The process by which membrane channel function is altered by drugs and biochemicals is termed "channel modulation". Functional channelomic studies also includes study of diseases resulting from their mis-function. Such a disease is termed a channelopathy.
The precise function of the prion protein is not known, but there is substantial evidence that it serves as a copper-dependent antioxidant.[