TOMOSYN - A SYNTAXIN-1-BINDING PROTEIN THAT FORMS A NOVEL COMPLEX IN THE NEUROTRANSMITTER RELEASE PROCESS

Syntaxin-1 is a component of the synaptic vesicle docking and/or membr ane fusion soluble N-etyhlmaleimide-sensitive factor attachment recept or (SNARE) complex (75 and 20S complexes) in nerve terminals, Syntaxin -1 also forms a heterodimer with Munc18/n-Sec1/rbSec1 in a complex tha t is distinct from the 75 and 20S complexes. In this report, we identi fy a novel syntaxin-1-binding protein, tomosyn, that is capable of dis sociating Munc18 from syntaxin-1 and forming a novel 10S complex with syntaxin-1, soluble N-etyhlmaleimide-sensitive factor attachment (SNAP ) 25, and synaptotagmin. The 130 kDa isoform of tomosyn is specificall y expressed in brain, where its distribution partly overlaps with that of syntaxin-1 in nerve terminals. High level expression of either syn taxin-1 or tomosyn results in a specific reduction in Ca2+-dependent e xocytosis from PC12 cells. These results suggest that tomosyn is an im portant component in the neurotransmitter release process where it may stimulate SNARE complex formation.