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First published online 4 August 2009
doi: 10.1242/jcs.052795

Journal of Cell Science 122, 3145-3152 (2009)
Published by The Company of Biologists 2009
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Research Article

GAK, a regulator of clathrin-mediated membrane traffic, also controls centrosome integrity and chromosome congression

Hiroyuki Shimizu, Ippei Nagamori*, Norikazu Yabuta and Hiroshi Nojima{ddagger}

Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Yamadaoka 3-1, Suita City, Osaka 565-0871, Japan

{ddagger} Author for correspondence (snj-0212{at}biken.osaka-u.ac.jp)

Accepted 15 June 2009

Cyclin G-associated kinase (GAK) is an association partner of clathrin heavy chain (CHC) and is essential for clathrin-mediated membrane trafficking. Here, we report two novel functions of GAK: maintenance of proper centrosome maturation and of mitotic chromosome congression. Indeed, GAK knockdown by siRNA caused cell-cycle arrest at metaphase, which indicates that GAK is required for proper mitotic progression. We found that this impaired mitotic progression was due to activation of the spindle-assembly checkpoint, which senses protruded, misaligned or abnormally condensed chromosomes in GAK-siRNA-treated cells. GAK knockdown also caused multi-aster formation, which was due to abnormal fragmentation of pericentriolar material, but not of the centrioles. Moreover, GAK and CHC cooperated in the same pathway and interacted in mitosis to regulate the formation of a functional spindle. Taken together, we conclude that GAK and clathrin function cooperatively not only in endocytosis, but also in mitotic progression.

Key words: Centrosome, Clathrin, Mitosis, Plk1, Tubulin, GAK


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