Syntaxin Function

Synaptotagmins Membrane proteins with at least 15 isoforms that contain C2 domains bind Ca2+ and phospholipids and interact with neurexins, AP2 and syntaxins. Synaptotagmins 1 and 2 may function as Ca2+ sensors in fast Ca2+-dependent neurotransmitter release... 

Neurexins a protein kinase. A component of active zones that interact with RIM, syntaxin and other proteins. Cell surface proteins with more than 1,000 isoforms generated by alternative splicing from three genes. Neurexins include one of the receptors for aratrotoxin and may function in cell-cell recognition between neurons. 

Other proteins are also needed. All cell fusion processes seem to require regulatory proteins that are essential to neurotransmission in the nematode C. elegans. Two of these are encoded by the nematode genes unc-13 and unc-18. The corresponding mammalian proteins munc-13 and munc-18 interact with syntaxin and are essential for exocytosis of synaptic vesicles.572 575 An ATPase is also needed for correct functioning of the SNARE complex574 as are other additional proteins.570... 

Qb-, Qc- and R-SNAREs (Bock and Scheller 2001). Following this classification, syntaxin 1A, SNAP-25, and synaptobrevin 2 represent the Qa-, Qb- and Qc-, and R-SNAREs, respectively (Fasshauer et al. 1998). It turned out later that actually all functional SNARE complexes assigned to trafficking steps in yeast and mammals have a QaQbQcR-composition (Hong 2005 Jahn and Scheller 2006). 

In addition to the proteins discussed above, neuronal SNAREs were reported to interact with numerous other proteins in a specific manner, but in most cases both the structural basis and the biological function of these interactions need to be defined. For instance, synaptophysin, a membrane protein of synaptic vesicles, forms a complex with synaptobrevin in which synaptobrevin is not available for interactions with its partner SNAREs syntaxin 1A and SNAP-25, suggesting that this complex represents a reserve pool of recruitable synaptobrevin (Becher et al. 1999) or regulates interactions between the vesicle-associated synaptobrevin and the plasmalem-mal SNAREs. Alternatively, it has been suggested that this complex is involved in synaptobrevin sorting to synaptic vesicles. 

Blier P, Bouchard C (1993) Functional characterization of a 5-HT3 receptor which modulates the release of 5-HT in the guinea-pig brain. Br J Pharmacol 108 13-22 Boczan J, Leenders AG, Sheng ZH (2004) Phosphorylation of syntaphilin by cAMP-dependent protein kinase modulates its interaction with syntaxin-1 and annuls its inhibitory effect on vesicle exocytosis. J Biol Chem 279 18911-19... 

Pagan, J.K., Wylie, F.G., Joseph, S., Widberg, C., Bryant, N.J., James, D.E., Stow, J.L. The t-SNARE syntaxin 4 is regulated during macrophage activation to function in membrane traffic and cytokine secretion. Curr Biol 13 (2003) 156-160. 

Pajonk, S., Kwon, C., Clemens, N., Panstmga, R., Schulze-Lefert, P. Activity determinants and functional specialization of Arabidopsis PEN1 syntaxin in innate immunity. J Biol Chem 283 (2008)26974-26984. 

Dual modes of Muncl8-1/SNARE interactions are coupled by 41. functionally critical binding to syntaxin-lN terminus. J. Neurosci. 2007 27 12147-55. 42. 

Broadie K, Prokop A, Bellen HI, O Kane CJ, Schulze KL, 43. Sweeney ST. Syntaxin and synaptobrevin function downstream... 

It is now well established that in vivo efficient membrane fusion requires the interaction of small cytoplasmically exposed membrane proteins called soluble N-ethylmaleimide sensitive factor (NSF) attachment receptors (SNAREs) (Sollner et al., 1993). For synaptic vesicle exocytosis, the relevant SNAREs are synaptobrevin/ vesicle-associated membrane protein (VAMP) 1 and 2, syntaxin 1, and synaptosome-associ-ated protein of 25,000 daltons (SNAP-25). Synaptobrevins/ VAMPs are localized primarily on synaptic vesicles, while syntaxin and SNAP-25 are localized primarily on the plasma membrane. Fusion is driven by the progressive zippering of vesicle and plasma membrane SNAREs forming a four-helix bundle (Sutton et al., 1998). Although many other proteins appear to play critical roles in synaptic vesicle exocytosis, it seems likely that SNAREs are the minimal machinery required for fusion (Weber et al., 1998). Once assembled, SNARE complexes are disassembled by NSF, which functions in conjunction with SNAP proteins. 

Braun JEA, Fritz BA, Wong SME, Lowe AW (1994) Identification of a vesicle-associated membrane protein (VAMP-like) membrane protein in zymogen granules of the rat exocryne pancreas. In J. Biol. Chem. 269 5328-35 Brennwald P, Kearns B, Champion K, Keranen S, Bankaitis V, Novick P (1994) Sec9 is a SNAP-25-like component of a yeast SNARE complex that may be the effector of Sec4 function in excytosis. In Cell 79 245—58 Broadie K, Prokop A, Bellen HJ, O Kane C, Schulze KL, Sweeney ST (1995) Syntaxin and synaptobrevin function downstream of vesicle docking in Drosophila. In Neuron 15 663-73... 

---