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Direct interaction of SNARE complex binding protein synaphin/complexin with calcium sensor synaptotagmin 1.

Authors: Tokumaru, H  Shimizu-Okabe, C  Abe, T 
Citation: Tokumaru H, etal., Brain Cell Biol. 2008 Dec;36(5-6):173-89. doi: 10.1007/s11068-008-9032-9. Epub 2009 Jan 9.
Pubmed: (View Article at PubMed) PMID:19132534
DOI: Full-text: DOI:10.1007/s11068-008-9032-9

Although the binding of synaphin (also called complexin) to the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex is critical for synaptic vesicle exocytosis, the exact role of synaphin remains unclear. Here, we show that synaphin directly binds to synaptotagmin 1, a major Ca(2+) sensor for fast neurotransmitter release, in a 1:1 stoichiometry. Mapping of the synaphin site involved in synaptotagmin 1 binding revealed that the C-terminal region is essential for the interaction between these two proteins. Binding was sensitive to ionic strength, suggesting the involvement of charged residues in the C-terminus region. Mutation of the seven consecutive glutamic acid residues (residues 108-114) at the C-terminal region of synaphin to alanines or glutamines resulted in a dramatic reduction in synaptotagmin 1 binding activity. Furthermore, a peptide from the C-terminus of synaphin (residues 91-124) blocked the binding of synaptotagmin 1 to synaphin, an effect that was abolished by mutating the consecutive glutamic acid residues to alanine. Immunoprecipitation experiments with brain membrane extracts showed the presence of a complex consisting of synaphin, synaptotagmin 1, and SNAREs. We propose that synaphin recruits synaptotagmin 1 to the SNARE-based fusion complex and synergistically functions with synaptotagmin 1 in mediating fast synaptic vesicle exocytosis.

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CRRD Object Information
CRRD ID: 7205655
Created: 2013-01-10
Species: All species
Last Modified: 2013-01-10
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.