| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Research Abstract |
Synaptotagmin, a synaptic vesicle protein containing two C2 domains (C2A, C2B), is a putative Ca2+ sensor for neurotransmitter release that cooperates with SNARE complexes. Whereas experiments using soluble fragments have shown that synaptotagmin-SNARE interactions require Ca2+ binding to both C2 domains, Ca2+ binding to C2B is more critical for release. Therefore, it is still unknown how synaptotagmin transduces Ca2+ signals to SNARE-mediated exocytosis. In this study, we showed that Ca2+ binding to the C2B domain released synaptotagmin from syntaxin within SNARE complexes at 37 degrees Celsius when using native proteins, proteins expressed in mammalian cells, or bacterial-expressed proteins reconstituted into liposomes. Together with the previous functional analysis, our findings indicate that synaptotagmin dissociates from SNARE complexes by Ca2+ during transmitter release and, thus, acts as a clamp that suppresses SNARE activity until Ca2+ influx.
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