SNARE family

Stimulus-evoked, calcium-dependent release of acetylcholine (ACh) from the cholinergic synapse normally occurs through the formation of a fusion complex between ACh-containing vesicles and the intracellular leaflet of the nerve terminal membrane (Amon et al., 2001). This synaptic vesicle fusion complex consists of several proteins of the SNARE family, including a 25 kDa synaptosomal associated protein (SNAP-25), vesicle-associated membrane protein (VAMP, or synaptobrevin), and the synaptic membrane protein syntaxin. Other SNARE proteins have been identified as components of membrane transport systems in yeast and mammals but have not been implicated as targets for BoNTs. Meanwhile, type A and E neurotoxins cleave SNAP-25 while types B, D, F, and G act on VAMP and type C1 toxin cleaves both syntaxin and SNAP-25. Neurotoxin-mediated cleavage of any of these substrates disrupts the processes involved in the exocytotic release of ACh and leads to flaccid paralysis of the affected skeletal muscles. 

Let me count the ways. Each intracellular fusion of a vesicle with a membrane requires a SNARE protein on the vesicle (called the v-SNARE) and a SNARE protein on the target membrane (called the t-SNARE). Assume that a genome encodes 21 members of the v-SNARE family and 7 members of the t-SNARE family. With the assumption of no specificity, how many potential v-SNARE-t-SNARE interactions could take place ... 

Seel A member of a family of proteins that attach to t-SNAREs and are displaced from them by Rab proteins, thereby allowing v-SNARE-t-SNARE interactions to occur. 

Step 5 Vesicle targeting is achieved via members of a family of integral proteins, termed v-SNAREs, that tag the vesicle during its budding. v-SNAREs pair with cognate t-SNAREs in the target membrane to dock the vesicle. 

Membrane fusion consists of merging two negatively charged phospholipid bilayers, and thus requires overcoming a major energy barrier (Jahn et al., 2003). SNARE proteins represent a family of membrane proteins that are present on opposing membranes destined to fuse. As first proposed by Jahn, Heuser, Rothman and colleagues... 

Once the vesicles carrying GLUT4 have arrived at the plasma membrane, they must fuse with the membrane. For that purpose the cell uses a machinery, the comjjonents of which have been identified in recent years. Among the proteins that participate in the docking process, the SNARE protein family of receptors is of central importance, as was shown in J. Rothman s laboratory (Fig. 8.3).2 ... 

A family of protein acyltransferases (PATs) is responsible for S-acylation of proteins in cells (S. Lobo, 2002 A. Roth, 2002) [8]. Members of this family are characterized by the presence of a cysteine-rich domain containing a DHHC (Asp-His-His-Cys) motif. PATs are polytopic membrane proteins with the putative catalytic DHHC motif localized to a cytoplasmic loop between transmembrane spans. Some PATs function alone whereas others, such as the yeast Ras PAT Erf2, require a cytoplasmic protein, Erf4, for activity. It is likely that particular classes of substrate have a dedicated PAT that accounts for most, if not all, of their S-acylation. For example, Swflp modifies SNARE proteins and other monotopic membrane proteins with a juxtamembrane cysteine residue. The yeast vacuolar protein Vac8 is mainly S-acylated by the vacuolar DHHC protein Pfa3 (J.E. Smotrys,... 

SNARE proteins A family of enzymes that facilitate the fusion of biological vesicles with cell membranes. SNARE = Soluble N-ethylmaleimide-sensitive factor attachment protein receptor. 

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