Clathrin heavy chain mediates TACC3 targeting to mitotic spindles to
ensure spindle stability |
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| Authors: | Chiou-Hong Lin Chi-Kuo Hu Hsiu-Ming Shih |
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| Institution: | 1.Graduate Institute of Life Sciences,
National Defense Medical Center, and 2.Institute of Biomedical Sciences, Academia Sinica,
Taipei 11529, Taiwan;3.Department of Systems Biology, and 4.Graduate Program in Biological and Biomedical
Sciences, Harvard Medical School, Boston, MA 02115 |
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| Abstract: | Mitotic spindles play essential roles in chromosome congression and segregation
during mitosis. Aurora A regulates spindle assembly in part via phosphorylating
human TACC3 on S558, which triggers TACC3 relocalization to mitotic spindles and
stabilizes microtubules (MTs). In this study, we identified clathrin heavy chain
(CHC) as an adaptor protein to recruit S558-phosphorylated TACC3 onto the
spindle during mitosis for MT stabilization. CHC binds phospho-S558 TACC3 via
its linker domain and first CHC repeat. CHC depletion or mutation on
phospho-TACC3 binding abrogates TACC3 spindle relocalization. Depletion of
either or both CHC and TACC3 yields similar defective phenotypes: loss of ch-TOG
on spindles, disorganized spindles, and chromosome misalignment with comparable
mitotic delay. Our findings elucidate the association between aurora A
phosphorylation and spindle apparatus and demonstrate that regulation from
aurora A is mediated by CHC in recruiting phospho-TACC3 and subsequently ch-TOG
to mitotic spindles. |
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