Clathrin heavy chain mediates TACC3 targeting to mitotic spindles to ensure spindle stability.
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.
Lin
Chiou-Hong
CH
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11529, Taiwan.
Hu
Chi-Kuo
CK
Shih
Hsiu-Ming
HM
D064127:Aurora Kinases; D033922:Clathrin Heavy Chains / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000378:metabolism*; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D008941:Spindle Apparatus / Q000378:metabolism*
C454180:CKAP5 protein, human; D008869:Microtubule-Associated Proteins; C120551:TACC3 protein, human; D033922:Clathrin Heavy Chains; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases