RGD Reference Report - Myosin-Va regulates exocytosis through the submicromolar Ca2+-dependent binding of syntaxin-1A. - Rat Genome Database

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Pathways

Myosin-Va regulates exocytosis through the submicromolar Ca2+-dependent binding of syntaxin-1A.

Authors: Watanabe, M  Nomura, K  Ohyama, A  Ishikawa, R  Komiya, Y  Hosaka, K  Yamauchi, E  Taniguchi, H  Sasakawa, N  Kumakura, K  Ushiki, T  Sato, O  Ikebe, M  Igarashi, M 
Citation: Watanabe M, etal., Mol Biol Cell. 2005 Oct;16(10):4519-30. Epub 2005 Jul 19.
RGD ID: 1581734
Pubmed: PMID:16030255   (View Abstract at PubMed)
PMCID: PMC1237061   (View Article at PubMed Central)
DOI: DOI:10.1091/mbc.E05-03-0252   (Journal Full-text)

Myosin-Va is an actin-based processive motor that conveys intracellular cargoes. Synaptic vesicles are one of the most important cargoes for myosin-Va, but the role of mammalian myosin-Va in secretion is less clear than for its yeast homologue, Myo2p. In the current studies, we show that myosin-Va on synaptic vesicles interacts with syntaxin-1A, a t-SNARE involved in exocytosis, at or above 0.3 microM Ca2+. Interference with formation of the syntaxin-1A-myosin-Va complex reduces the exocytotic frequency in chromaffin cells. Surprisingly, the syntaxin-1A-binding site was not in the tail of myosin-Va but rather in the neck, a region that contains calmodulin-binding IQ-motifs. Furthermore, we found that syntaxin-1A binding by myosin-Va in the presence of Ca2+ depends on the release of calmodulin from the myosin-Va neck, allowing syntaxin-1A to occupy the vacant IQ-motif. Using an anti-myosin-Va neck antibody, which blocks this binding, we demonstrated that the step most important for the antibody's inhibitory activity is the late sustained phase, which is involved in supplying readily releasable vesicles. Our results demonstrate that the interaction between myosin-Va and syntaxin-1A is involved in exocytosis and suggest that the myosin-Va neck contributes not only to the large step size but also to the regulation of exocytosis by Ca2+.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Myo5aRatactin filament-based movement  IDA  RGD 
Myo5aRatregulation of exocytosis  IMP  RGD 
Stx1aRatregulation of exocytosis  IMP  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Stx1aRatactomyosin  IDA  RGD 
Myo5aRatactomyosin, myosin complex part  IDA  RGD 
Snap25RatSNARE complex  IDA  RGD 
Vamp2RatSNARE complex  IDA  RGD 
Myo5aRatsynaptic vesicle  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Myo5aRatATP binding  IDA  RGD 
Myo5aRatATP-dependent protein binding  IPIStx1a (Rattus norvegicus) RGD 
Stx1aRatATP-dependent protein binding  IPIMyo5a (Rattus norvegicus) RGD 
Myo5aRatcalcium-dependent protein binding  IPIStx1a (Rattus norvegicus) RGD 
Stx1aRatcalcium-dependent protein binding  IPIMyo5a (Rattus norvegicus) RGD 
Myo5aRatmicrofilament motor activity  IDA  RGD 
Snap25Ratmyosin binding  IPIMyo5a (Rattus norvegicus) RGD 
Stx1aRatmyosin binding  IPIMyo5a (Rattus norvegicus) RGD 
Vamp2Ratmyosin binding  IPIMyo5a (Rattus norvegicus) RGD 
Stx1aRatmyosin head/neck binding  IPIMyo5a (Rattus norvegicus) RGD 
Myo5aRatprotein-containing complex binding  IDA heterodimerizationRGD 
Stx1aRatprotein-containing complex binding  IDA heterodimerizationRGD 
Stx1aRatprotein-macromolecule adaptor activity  IPIVamp2 (Rattus norvegicus) RGD 
Stx1aRatprotein-macromolecule adaptor activity  IPISnap25 (Rattus norvegicus) RGD 
Stx1aRatprotein-macromolecule adaptor activity  IPIMyo5a (Rattus norvegicus) RGD 
Myo5aRatSNARE binding  IPISnap25 (Rattus norvegicus) RGD 
Myo5aRatSNARE binding  IPIVamp2 (Rattus norvegicus) RGD 
Stx1aRatSNARE binding  IPISnap25 (Rattus norvegicus) RGD 
Stx1aRatSNARE binding  IPIVamp2 (Rattus norvegicus) RGD 
Myo5aRatsyntaxin-1 binding  IPIStx1a (Rattus norvegicus) RGD 
Snap25Ratsyntaxin-1 binding  IPIStx1a (Rattus norvegicus) RGD 
Vamp2Ratsyntaxin-1 binding  IPIStx1a (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Myo5a  (myosin VA)
Snap25  (synaptosome associated protein 25)
Stx1a  (syntaxin 1A)
Vamp2  (vesicle-associated membrane protein 2)


Additional Information