β phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs
β phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs
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DOI：
10.1016/s0092-8674(01)00635-3
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发表时间：
2002-01-11
期刊：
影响因子：
64.5
通讯作者：
Brose, N
中科院分区：
文献类型：
--
作者：
Rhee, JS;Betz, A;Brose, N
Munc 13 -1是一种突触前蛋白，在突触小泡启动中起重要作用。它含有二酰基甘油（DAG）/β佛波酯结合C-1结构域，是DAG第二信使途径的潜在靶点，可能与PKC平行作用。使用表达DAG/β佛波酯结合缺陷型Munc 13 -1（H567 K）变体而不是野生型蛋白的转基因小鼠，我们确定了PKC和Munc 13 -1对DAG/β佛波酯依赖性调节神经递质释放的相对贡献。我们发现，Munc 13是海马神经元突触前主要的DAG/β佛波酯受体。第二信使通过DAG/β佛波醇酯结合C-1结构域调节Munc 13 -1活性对于突触功效和存活的使用依赖性改变是必不可少的。
Munc13-1 is a presynaptic protein with an essential role in synaptic vesicle priming. It contains a diacylglycerol (DAG)/beta phorbol ester binding C-1 domain and is a potential target of the DAG second messenger pathway that may act in parallel with PKCs. Using genetically modified mice that express a DAG/beta phorbol ester binding-deficient Munc13-1(H567K) variant instead of the wild-type protein, we determined the relative contribution of PKCs and Munc13-1 to DAG/beta phorbol ester-dependent regulation of neurotransmitter release. We show that Munc13s are the main presynaptic DAG/beta phorbol ester receptors in hippocampal neurons. Modulation of Munc13-1 activity by second messengers via the DAG/beta phorbol ester binding C-1 domain is essential for use-dependent alterations of synaptic efficacy and survival.