1998 Fiscal Year Final Research Report Summary
Functions and modes of action of proteins with C2 domains in Ca^<2+>-dependent
| Project/Area Number |
09670153
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
SASAKI Takuya Osaka University Medical School, Associate Professor, 医学部, 助教授 (40241278)
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| Project Period (FY) |
1997 – 1998
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| Keywords | C2 domain / Rabphilin-3A / neurotransmitter release / Doc2 / Munc13 / long-term potentiation / Muncl3 / Rabaptin-5 |
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| Research Abstract |
The C2 domain has first been identified in a conventional type of protein kinase C.The C2 domain interacts with Ca^<2+> and phospholipids.The interactions of protein kinase C with these factors through the C2 domain are essential for its activation.Protein kinase C has one C2 domain, but proteins having two C2-like domains have recently identified.Accumulating evidence suggests that proteins having two C2-like domains are implicated in Ca_<+1> -dependent neurotrans- mitter release.These include synaptotagmin, Munc13, rabphilin-3A, and Doc2.Of these proteins, rabphilin-3A and Doc2 were discovered in our laboratory.
During this support from 1997 to 1998, we have focused on studying the functions and modes of actions of rabphilin-3A and Doc2 in neurotransmitter release.The results obtained are as follows :
(1) Electrophysiological study using the squid giant axon system indicates that rabphilin-3A is involved in Ca^<2+> -dependent neurotransmitter release.
(2) We have found that Doc2 directly interacts with Munc13, which is localized at the presynaptic plasma membrane and is implicated in Ca^<2+> -dependent neuro- transmitter release.We have found that the region localized near the N-terminus of Doc2, named Mid (Munc13-interacting domain), directly binds to a region between the two C2-like domains of Munc13, named Did (Doc2-interacting domain).The Doc2-Munc13 interaction is enhanced by the binding of diacylglycerol or phorbol ester to the C1-like domain of Munc13.
(3) Electrophysiological study using cultured rat superior cervical ganglion neurons indicates that the Doc2-Munc13 interaction is involved in Ca^<2+> -dependent neurotransmitter release.Electrophysiological study using the CA1 region of hippocampal slices of Doc2 null mutant mice indicates that Doc2 is not essential for basal neurotransmission but is involved in short-term plasticity and long-term potentiation.
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Research Products
(30 results)
