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Munc18–1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation
Author(s) -
Toonen Ruud F. G.,
De Vries Klaas Jan,
Zalm Robbert,
Südhof Thomas C.,
Verhage Matthijs
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03128.x
Subject(s) - syntaxin , snare complex , syntaxin 3 , microbiology and biotechnology , exocytosis , stx1a , munc 18 , lipid bilayer fusion , vesicle fusion , knockout mouse , biology , chemistry , synaptic vesicle , secretion , vesicle , membrane , biochemistry , receptor
Munc18–1, a member of the Sec1/Munc18 (SM) protein family, is essential for synaptic vesicle exocytosis. Munc18–1 binds tightly to the SNARE protein syntaxin 1, but the physiological significance and functional role of this interaction remain unclear. Here we show that syntaxin 1 levels are reduced by 70% in munc18–1 knockout mice. Pulse‐chase analysis in transfected HEK293 cells revealed that Munc18–1 directly promotes the stability of syntaxin 1, consistent with a chaperone function. However, the residual syntaxin 1 in munc18–1 knockout mice is still correctly targeted to synapses and efficiently forms SDS‐resistant SNARE complexes, demonstrating that Munc18–1 is not required for syntaxin 1 function as such. These data demonstrate that the Munc18–1 interaction with syntaxin 1 is physiologically important, but does not represent a classical chaperone‐substrate relationship. Instead, the presence of SNARE complexes in the absence of membrane fusion in munc18–1 knockout mice indicates that Munc18–1 either controls the spatially correct assembly of core complexes for SNARE‐dependent fusion, or acts as a direct component of the fusion machinery itself.