β佛波醇酯和二酰基甘油诱导的递质释放增强是由Munc13介导的，而非蛋白激酶C。
Beta phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs.
作者信息
Rhee Jeong Seop, Betz Andrea, Pyott Sonja, Reim Kerstin, Varoqueaux Frederique, Augustin Iris, Hesse Dörte, Südhof Thomas C, Takahashi Masami, Rosenmund Christian, Brose Nils
机构信息
Abteilung Membranbiophysik, Max-Planck-Institut für Biophysikalische Chemie, Am Fassberg 11, D-37077 Göttingen, Bundesrepublik Deutschland.
出版信息
Cell. 2002 Jan 11;108(1):121-33. doi: 10.1016/s0092-8674(01)00635-3.
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.
Munc13-1是一种突触前蛋白，在突触小泡启动过程中起关键作用。它含有一个二酰基甘油（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，可能与蛋白激酶C（PKC）平行发挥作用。通过使用表达缺乏DAG/β佛波酯结合能力的Munc13-1(H567K)变体而非野生型蛋白的基因改造小鼠，我们确定了PKC和Munc13-1对DAG/β佛波酯依赖性神经递质释放调节的相对贡献。我们发现Munc13s是海马神经元中主要的突触前DAG/β佛波酯受体。第二信使通过DAG/β佛波酯结合C(1)结构域对Munc13-1活性的调节对于突触效能和存活的使用依赖性改变至关重要。
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