TY - JOUR
T1 - Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles
AU - Tomizawa, Kazuhito
AU - Sunada, Satoshi
AU - Lu, Yun Fei
AU - Oda, Yoshiya
AU - Kinuta, Masahiro
AU - Ohshima, Toshio
AU - Saito, Taro
AU - Wei, Fan Yan
AU - Matsushita, Masayuki
AU - Li, Sheng Tian
AU - Tsutsui, Kimiko
AU - Hisanaga, Shin Ichi
AU - Mikoshiba, Katsuhiko
AU - Takei, Kohji
AU - Matsui, Hideki
PY - 2003/11/24
Y1 - 2003/11/24
N2 - 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.
AB - 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.
KW - Cyclin-dependent kinase
KW - Endocytic protein
KW - P35
KW - Presynapse
KW - Synaptosome
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UR - http://www.scopus.com/inward/citedby.url?scp=10744228914&partnerID=8YFLogxK
U2 - 10.1083/jcb.200308110
DO - 10.1083/jcb.200308110
M3 - Article
C2 - 14623869
AN - SCOPUS:10744228914
SN - 0021-9525
VL - 163
SP - 813
EP - 824
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -