Tomosyn

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In biology, tomosyn is a protein with approximately 1,100 amino acids. Two functional domains were originally identified, including one which binds to syntaxin, but recent crystallization of the yeast homolog Sro7 (Hattendorf et al 2007) revealed that tomosyn likely has three functional domains: one WD40 domain and one syntaxin-binding domain, as previously recognized, but also another WD40 domain. The study by Hattendorf et al also suggested that tomosyn's 'syntaxin binding domain' is not the reason tomosyn is inhibitory for neurotransmitter release, as originally proposed. Positional cloning by Dybbs et al. suggested that tomosyn might inhibit neurotransmitter secretion in Caenorhabditis elegans neurons. This hypothesis was tested and confirmed by Gracheva et al (2006), who showed that tomosyn specifically inhibits synaptic vesicle priming -- the biochemical step immediately preceding vesicle fusion and neurotransmitter release.

[edit] References

• Hattendorf DA, Andreeva A, Gangar A, Brennwald PJ, and Weis WI (2007) Structure of the yeast polarity protein Sro7 reveals

a SNARE regulatory mechanism. Nature 446:567-571

• Dybbs M, Ngai J, Kaplan JM (2005) Using Microarrays to Facilitate Positional Cloning: Identification of Tomosyn as an Inhibitor of Neurosecretion. PLoS Genet 1(1): e2

• Gracheva EO, Burdina AO, Holgado AM, Berthelot-Grosjean M, Ackley BD, Hadwiger G, Nonet ML, Weimer RM, Richmond JE. Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans. PLoS Biol. 2006 Jul;4(8):e261.