GAK, a regulator of clathrin-mediated membrane traffic, also controls centrosome integrity and chromosome congression.
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.
Shimizu
Hiroyuki
H
Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, Suita City, Osaka, Japan.
Nagamori
Ippei
I
Yabuta
Norikazu
N
Nojima
Hiroshi
H
D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D002875:Chromosomes / Q000235:genetics* / Q000378:metabolism; D002966:Clathrin / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism
D002966:Clathrin; D047908:Intracellular Signaling Peptides and Proteins; C486325:GAK protein, human; D017346:Protein Serine-Threonine Kinases