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Functions and modes of action of proteins with C2 domains in Ca^<2+>-dependent

Ca^<2>依赖性的具有C2结构域的蛋白质的功能和作用方式

基本信息

批准号：
09670153
负责人：
SASAKI Takuya
金额：
$ 2.3万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670153/
关键词：
C2 domain Rabphilin-3A neurotransmitter release Doc2 Munc13 long-term potentiation Muncl3 Rabaptin-5 Munc13 ダイニン LTP

项目摘要

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.

C2结构域首先在传统类型的蛋白激酶C中被发现。C2结构域与钙离子和磷脂相互作用。蛋白激酶C通过C2结构域与这些因子的相互作用是其激活的关键。蛋白激酶C有一个C2结构域，但最近发现有两个C2结构域的蛋白质。越来越多的证据表明，具有两个类似C2结构域的蛋白质与Ca_1&gt；-依赖神经递质的释放，包括突触素、Munc13、RabPhilin-3A和Doc2。在这些蛋白中，RabPhilin-3A和Doc2是我们实验室在1997-1998年的支持下发现的。在此期间，我们重点研究了RabPhilin-3A和Doc2在神经递质释放中的功能和作用方式。结果如下：(1)利用鱿鱼巨轴突系统进行的电生理研究表明RabPhilin-3A参与了Ca^&lt；(2)我们发现Doc2与Munc13直接相互作用，Munc13定位于突触前质膜，与Ca~(2+)和GT；我们发现Doc2-Munc13相互作用区域直接与Munc13的两个类C2结构域之间的区域DID(DID)结合。二酰甘油或佛波酯与Munc13的C1样结构域结合可增强Doc2-Munc13的相互作用。(3)培养的大鼠颈上神经节神经元的电生理研究表明，Doc2-Munc13相互作用参与了钙离子的调节；-依赖神经递质的释放。使用Doc2缺失突变小鼠海马片CA1区的电生理学研究表明，Doc2对基础神经传递不是必需的，但参与了短期可塑性和长期增强。