Munc18-bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes.

Abstract:

:Munc18-1, a protein essential for regulated exocytosis in neurons and neuroendocrine cells, belongs to the family of Sec1/Munc18-like (SM) proteins. In vitro, Munc18-1 forms a tight complex with the SNARE syntaxin 1, in which syntaxin is stabilized in a closed conformation. Since closed syntaxin is unable to interact with its partner SNAREs SNAP-25 and synaptobrevin as required for membrane fusion, it has hitherto not been possible to reconcile binding of Munc18-1 to syntaxin 1 with its biological function. We now show that in intact and exocytosis-competent lawns of plasma membrane, Munc18-1 forms a complex with syntaxin that allows formation of SNARE complexes. Munc18-1 associated with membrane-bound syntaxin 1 can be effectively displaced by adding recombinant synaptobrevin but not syntaxin 1 or SNAP-25. Displacement requires the presence of endogenous SNAP-25 since no displacement is observed when chromaffin cell membranes from SNAP-25-deficient mice are used. We conclude that Munc18-1 allows for the formation of a complex between syntaxin and SNAP-25 that serves as an acceptor for vesicle-bound synaptobrevin and that thus represents an intermediate in the pathway towards exocytosis.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Zilly FE,Sørensen JB,Jahn R,Lang T

doi

10.1371/journal.pbio.0040330

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

e330

issue

10

eissn

1544-9173

issn

1545-7885

pii

06-PLBI-RA-0799R2

journal_volume

4

pub_type

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