RGD Reference Report - Involvement of Rab3A in vesicle priming during exocytosis: interaction with Munc13-1 and Munc18-1. - Rat Genome Database

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Involvement of Rab3A in vesicle priming during exocytosis: interaction with Munc13-1 and Munc18-1.

Authors: Huang, Chien-Chang  Yang, De-Ming  Lin, Chung-Chih  Kao, Lung-Sen 
Citation: Huang CC, etal., Traffic. 2011 Oct;12(10):1356-70. doi: 10.1111/j.1600-0854.2011.01237.x. Epub 2011 Jul 20.
RGD ID: 14390056
Pubmed: PMID:21689256   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1600-0854.2011.01237.x   (Journal Full-text)

Rab3A is a small G-protein of the Rab family that is involved in the late steps of exocytosis. Here, we studied the role of Rab3A and its relationship with Munc13-1 and Munc18-1 during vesicle priming. Phorbol 12-myristate 13-acetate (PMA) is known to enhance the percentage of fusion-competent vesicles and this is mediated by protein kinase C (PKC)-independent Munc13-1 activation and PKC-dependent dissociation of Munc18-1 from syntaxin 1a. Our results show that the effects of PMA varied in cells overexpressing Rab3A or mutants of Rab3A and in cells with Rab3A knockdown. When Munc13-1 was overexpressed in Rab3A knockdown cells, secretion was completely inhibited. In cells overexpressing a Rab-interacting molecule (RIM)-binding deficient Munc13-1 mutant, 128-Munc13-1, the effects of Rab3A on PMA-induced secretion was abolished. The effect of PMA, which disappeared in cells overexpressing GTP-Rab3A (Q81L), could be reversed by co-expressing Munc18-1 but not its mutant R39C, which is unable to bind to syntaxin 1a. In cells overexpressing Munc18-1, manipulation of Rab3A activity had no effect on secretion. Finally, Munc18-1 enhanced the dissociation of Rab3A, and such enhancement correlated with exocytosis. In summary, our results support the hypothesis that the Rab3A cycle is coupled with the activation of Munc13-1 via RIM, which accounts for the regulation of secretion by Rab3A. Munc18-1 acts downstream of Munc13-1/RIM/Rab3A and interacts with syntaxin 1a allowing vesicle priming. Furthermore, Munc18-1 promotes Rab3A dissociation from vesicles, which then results in fusion.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of synaptic vesicle priming involved_inIDA 14390056; 14390056; 14390056PMID:21689256UniProt 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:P6176514390056PMID:21689256UniProt 
protein binding enablesIPIUniProtKB:P6301214390056PMID:21689256UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Rab3a  (RAB3A, member RAS oncogene family)
Stxbp1  (syntaxin binding protein 1)
Unc13a  (unc-13 homolog A)


Additional Information