Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles

Kazuhito Tomizawa, Satoshi Sunada, Yun Fei Lu, Yoshiya Oda, Masahiro Kinuta, Toshio Ohshima, Taro Saito, Fan Yan Wei, Masayuki Matsushita, Sheng Tian Li, Kimiko Tsutsui, Shin Ichi Hisanaga, Katsuhiko Mikoshiba, Kohji Takei, Hideki Matsui

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154 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)813-824
Number of pages12
JournalJournal of Cell Biology
Volume163
Issue number4
DOIs
Publication statusPublished - 2003 Nov 24

Keywords

  • Cyclin-dependent kinase
  • Endocytic protein
  • P35
  • Presynapse
  • Synaptosome

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Tomizawa, K., Sunada, S., Lu, Y. F., Oda, Y., Kinuta, M., Ohshima, T., Saito, T., Wei, F. Y., Matsushita, M., Li, S. T., Tsutsui, K., Hisanaga, S. I., Mikoshiba, K., Takei, K., & Matsui, H. (2003). Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles. Journal of Cell Biology, 163(4), 813-824. https://doi.org/10.1083/jcb.200308110