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

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 process...

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173686/
https://www.ncbi.nlm.nih.gov/pubmed/14623869
http://dx.doi.org/10.1083/jcb.200308110
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author 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
author_facet 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
author_sort Tomizawa, Kazuhito
collection PubMed
description 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.
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spelling pubmed-21736862008-05-01 Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles 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 J Cell Biol Article 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. The Rockefeller University Press 2003-11-24 /pmc/articles/PMC2173686/ /pubmed/14623869 http://dx.doi.org/10.1083/jcb.200308110 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
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
Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles
title Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles
title_full Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles
title_fullStr Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles
title_full_unstemmed Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles
title_short Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles
title_sort cophosphorylation of amphiphysin i and dynamin i by cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173686/
https://www.ncbi.nlm.nih.gov/pubmed/14623869
http://dx.doi.org/10.1083/jcb.200308110
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