RGD Reference Report - Munc18-1 Regulates Early and Late Stages of Exocytosis via Syntaxin-independent Protein Interactions. - Rat Genome Database

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Munc18-1 Regulates Early and Late Stages of Exocytosis via Syntaxin-independent Protein Interactions.

Authors: Ciufo, LF  Barclay, JW  Burgoyne, RD  Morgan, A 
Citation: Ciufo LF, etal., Mol Biol Cell 2004 Nov 24;.
RGD ID: 1302922
Pubmed: PMID:15563604   (View Abstract at PubMed)
PMCID: PMC545880   (View Article at PubMed Central)
DOI: DOI:10.1091/mbc.E04-08-0685   (Journal Full-text)

Monitoring Editor: Keith Mostov Sec1/Munc18 (SM) proteins are involved in various intracellular membrane trafficking steps. Many SM proteins bind to appropriate syntaxin homologues involved in these steps, suggesting that SM proteins function as syntaxin chaperones. Organisms with mutations in SM genes, however, exhibit defects in either early (docking) or late (fusion) stages of exocytosis, implying that SM proteins may have multiple functions. To gain insight into the role of SM proteins, we introduced mutations modeled on those identified in C. elegans, D. melanogaste, and S. cerevisiae into mammalian Munc18-1. As expected, several mutants exhibited reduced binding to syntaxin1A. However, 3 mutants displayed wild-type syntaxin binding affinities, indicating syntaxin-independent defects. Expression of these mutants in chromaffin cells either increased the rate and extent of exocytosis or altered the kinetics of individual release events. This latter effect was associated with a reduced Mint binding affinity in one mutant, implying a potential mechanism for the observed alteration in release kinetics. Furthermore, this phenotype persisted when the mutation was combined with a second mutation that greatly reduced syntaxin binding affinity. These results clarify the data on the function of SM proteins in mutant organisms, and indicate that Munc18-1 controls multiple stages of exocytosis via both syntaxin-dependent and -independent protein interactions.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Stxbp3Ratvesicle docking involved in exocytosis  TAS  RGD 

Molecular Function

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Stxbp3Ratsyntaxin-1 binding  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Stxbp3  (syntaxin binding protein 3)

Additional Information