RGD Reference Report - Munc18-1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation. - Rat Genome Database

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Munc18-1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation.

Authors: Toonen, RF  De Vries, KJ  Zalm, R  Sudhof, TC  Verhage, M 
Citation: Toonen RF, etal., J Neurochem. 2005 Jun;93(6):1393-400.
RGD ID: 8554740
Pubmed: PMID:15935055   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1471-4159.2005.03128.x   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Stxbp1Ratprotein stabilization acts_upstream_of_or_withinIDA PMID:15935055MGI 

Objects Annotated

Genes (Rattus norvegicus)
Stxbp1  (syntaxin binding protein 1)


Additional Information