Physical and functional interaction of the active zone proteins, CAST, RIM1, and Bassoon, in neurotransmitter release.

Physical and functional interaction of the active zone proteins, CAST, RIM1, and Bassoon, in neurotransmitter release.
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神经递质释放中活性区蛋白,铸造,RIM1和低音的物理和功能相互作用。

DOI:
10.1083/jcb.200307101
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发表时间:
2004-01-19
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Takai Y
Takai Y
中科院分区:
其他
文献类型:
--
作者:
Takao-Rikitsu E;Mochida S;Inoue E;Deguchi-Tawarada M;Inoue M;Ohtsuka T;Takai Y

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我们最近在活性区(CAZ)相关蛋白CAST上分离出一种新型细胞基质,发现它直接结合另一种CAZ蛋白RIM1,并通过RIM1间接结合Munc13-1; RIM1 和 Munc13-1 直接相互结合,并参与突触小泡的启动。在这里,我们展示了迄今为止已知的所有 CAZ 蛋白在大脑中形成了一个大的分子复合物,包括 CAST、RIM1、Munc13-1、Bassoon 和 Piccolo。 RIM1和Bassoon分别直接与CAST的COOH末端和中心区域结合,形成三元复合物。短笛在结构上与巴松管相关,也与 CAST 的巴松管结合区结合。此外,显微注射的 CAST 的 RIM1 或巴松管结合区域会损害培养的颈上神经节神经元的突触传递。此外,RIM1 或巴松管的 CAST 结合域也会损害培养神经元的突触传递。这些结果表明,CAST 是 CAZ 结构的关键组成部分,并通过结合这些 CAZ 蛋白参与神经递质释放。
We have recently isolated a novel cytomatrix at the active zone (CAZ)–associated protein, CAST, and found it directly binds another CAZ protein RIM1 and indirectly binds Munc13-1 through RIM1; RIM1 and Munc13-1 directly bind to each other and are implicated in priming of synaptic vesicles. Here, we show that all the CAZ proteins thus far known form a large molecular complex in the brain, including CAST, RIM1, Munc13-1, Bassoon, and Piccolo. RIM1 and Bassoon directly bind to the COOH terminus and central region of CAST, respectively, forming a ternary complex. Piccolo, which is structurally related to Bassoon, also binds to the Bassoon-binding region of CAST. Moreover, the microinjected RIM1- or Bassoon-binding region of CAST impairs synaptic transmission in cultured superior cervical ganglion neurons. Furthermore, the CAST-binding domain of RIM1 or Bassoon also impairs synaptic transmission in the cultured neurons. These results indicate that CAST serves as a key component of the CAZ structure and is involved in neurotransmitter release by binding these CAZ proteins.
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发表时间: 2002-04-01
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巴松管是一种新型的锌指CAG/谷氨酰胺重复蛋白,选择性地定位于突触前神经末端的活性区域。
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