Clathrin promotes centrosome integrity in early mitosis through stabilization of centrosomal ch-TOG.

Clathrin promotes centrosome integrity in early mitosis through stabilization of centrosomal ch-TOG.
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DOI:
10.1083/jcb.201205116
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发表时间:
2012-08-20
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Brodsky FM
Brodsky FM
中科院分区:
其他
文献类型:
--
作者:
Foraker AB;Camus SM;Evans TM;Majeed SR;Chen CY;Taner SB;Corrêa IR Jr;Doxsey SJ;Brodsky FM

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Clathrin inactivation during S phase destabilizes the microtubule-binding protein ch-TOG, affecting its centrosomal localization and centrosome integrity during early mitosis. Clathrin depletion by ribonucleic acid interference (RNAi) impairs mitotic spindle stability and cytokinesis. Depletion of several clathrin-associated proteins affects centrosome integrity, suggesting a further cell cycle function for clathrin. In this paper, we report that RNAi depletion of CHC17 (clathrin heavy chain 17) clathrin, but not the CHC22 clathrin isoform, induced centrosome amplification and multipolar spindles. To stage clathrin function within the cell cycle, a cell line expressing SNAP-tagged clathrin light chains was generated. Acute clathrin inactivation by chemical dimerization of the SNAP-tag during S phase caused reduction of both clathrin and ch-TOG (colonic, hepatic tumor overexpressed gene) at metaphase centrosomes, which became fragmented. This was phenocopied by treatment with Aurora A kinase inhibitor, suggesting a centrosomal role for the Aurora A–dependent complex of clathrin, ch-TOG, and TACC3 (transforming acidic coiled-coil protein 3). Clathrin inactivation in S phase also reduced total cellular levels of ch-TOG by metaphase. Live-cell imaging showed dynamic clathrin recruitment during centrosome maturation. Therefore, we propose that clathrin promotes centrosome maturation by stabilizing the microtubule-binding protein ch-TOG, defining a novel role for the clathrin–ch-TOG–TACC3 complex.
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