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结构域首先在常规类型的蛋白激酶C中鉴定出来。C2结构域与Ca^<2+>和磷脂相互作用。蛋白激酶C与这些因素通过C2结构域的相互作用对于其激活而言是必不可少的。protein激酶C2蛋白具有一个C2域，但蛋白质均具有两个类似C2型的蛋白，该蛋白具有两种蛋白质。域与ca _ <+1>依赖性神经晶体释放有关。这些包括突触毒素，munc13，rabphilin-3a和doc2。这些蛋白质，rabphilin-3a和doc2在我们的实验室中发现了从1997年到1998年的支持，我们侧重于行动和模仿。神经递质的释放。获得的结果如下：（1）使用鱿鱼巨型轴突系统的电生理研究表明，rabphilin -3a与Ca^<2+>> - 依赖性神经递质释放有关。（2）我们发现Doc2与Munc13直接相互作用，而Munc13与Munc13相互作用，并且在2+insection <Is>+iSmbrane plassmaftip^ 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）使用培养大鼠上颈神经节神经元的电生理研究表明，DOC2-MUNC13相互作用与Ca^<2+>依赖性神经递质递质释放有关。电子生理研究的释放。使用Doc2-null Mutanter sement-dimes IS的CA1区域IS IS IS IS IS IS IS IS IS IS IS的CA1区域表示，IS均不重要。和长期增强。