SNARE proteins contribute to calcium cooperativity of synaptic transmission

SNARE proteins contribute to calcium cooperativity of synaptic transmission

Programs in ^*Developmental Biology, and ^†Cell Biology, The Hospital for Sick Children Research Institute, and Departments of ^‡Molecular and Medical Genetics, Zoology, and ^§Biochemistry, University of Toronto, 555 University Avenue, Toronto, ON, Canada M5G 1X8

Communicated by Richard H. Scheller, Stanford University, Stanford, CA (received for review September 18, 2000)

Abstract

A hallmark of calcium-triggered synaptic transmission is the cooperative relationship between calcium and the amount of transmitter released. This relationship is thought to be important for improving the efficiency of synaptic vesicle exocytosis. Although it is generally held that cooperativity arises from the interaction of multiple calcium ions with a single calcium-sensing molecule, the precise molecular basis of this phenomenon is not known. The SNARE proteins are known to be critical for synaptic vesicle exocytosis. We therefore tested for a contribution of SNARE proteins to cooperativity by genetically reducing the levels of syntaxin IA and neuronal-synaptobrevin in Drosophila. Surprisingly, we found that reducing these SNARE proteins also reduced Ca²⁺ cooperativity. Thus, SNARE proteins are important for determining the cooperative relationship between calcium and synaptic transmission.

Footnotes

↵ ¶ To whom reprint requests should be addressed. E-mail: wtrimble{at}sickkids.on.ca.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.250491397.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.250491397
Abbreviations:

Syt,

synaptotagmin I;

SNAP-25,

synaptosomal-associated protein of 25 kDa;

VAMP,

vesicle-associated membrane protein;

Syx,

syntaxin 1A;

n-Syb,

neuronal synaptobrevin;

EJC,

evoked junctional current;

mEJC,

miniature EJC