Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles.
Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles.
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CDK5对两亲蛋白I和Dynamin I的co磷酸化调节了网格蛋白介导的突触囊泡的内吞作用。
DOI：
10.1083/jcb.200308110
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发表时间：
2003-11-24
影响因子：
7.8
通讯作者：
Matsui, Hideki
中科院分区：
文献类型：
--
作者：
Tomizawa, Kazuhito;Sunada, Satoshi;Lu, Yun-Fei;Oda, Yoshiya;Kinuta, Masahiro;Ohshima, Toshio;Saito, Taro;Wei, Fan-Yan;Matsushita, Masayuki;Li, Sheng-Tian;Tsutsui, Kimiko;Hisanaga, Shin-ichi;Mikoshiba, Katsuhiko;Takei, Kohji;Matsui, Hideki
人们一直认为网格蛋白介导的内吞作用是由许多内吞蛋白的磷酸化和去磷酸化调节的，包括amphiphysin I和dynamin I。在这里，我们发现依赖Cdk5/p35的amphiphysin I和dynamin I的磷酸化在这一过程中起着关键作用。Cdk5抑制剂增强了电刺激诱导的海马神经元的内吞作用，p35缺陷小鼠神经元的内吞作用也增强了。Cdk5在体内和体外均可磷酸化amphiphysin I和dynamin I的富含脯氨酸的结构域。amphiphysin I的cdk5依赖性磷酸化抑制了与β-适应蛋白的关联。此外，动力蛋白I的磷酸化阻断了它与amphiphysin I的结合。在无细胞系统中，每种蛋白的磷酸化都减少了共聚成环的形成。此外，两种蛋白的磷酸化完全破坏了共聚成环的形成。最后，在p35缺陷小鼠中检测不到这两种蛋白的磷酸化。
It has been thought that clathrin-mediated endocytosis is regulated by phosphorylation and dephosphorylation of many endocytic proteins, including amphiphysin I and dynamin I. Here, we show that Cdk5/p35-dependent cophosphorylation of amphiphysin I and dynamin I plays a critical role in such processes. Cdk5 inhibitors enhanced the electric stimulation–induced endocytosis in hippocampal neurons, and the endocytosis was also enhanced in the neurons of p35-deficient mice. Cdk5 phosphorylated the proline-rich domain of both amphiphysin I and dynamin I in vitro and in vivo. Cdk5-dependent phosphorylation of amphiphysin I inhibited the association with β-adaptin. Furthermore, the phosphorylation of dynamin I blocked its binding to amphiphysin I. The phosphorylation of each protein reduced the copolymerization into a ring formation in a cell-free system. Moreover, the phosphorylation of both proteins completely disrupted the copolymerization into a ring formation. Finally, phosphorylation of both proteins was undetectable in p35-deficient mice.