Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 78, Issue 4, Pages 1765-1779Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-020-03614-8
Keywords
Aurora A; Dda3; Kif2A; MTUS1; Mitotic kinase; Mitotic spindle; Poleward microtubule flux
Categories
Funding
- Inserm, the CNRS, the Ligue Contre le Cancer 94/Val de Marne [2019]
- Institut Gustave Roussy
- Labex LERMIT
- GEFLUC association
- Fondation ARC
- Fonds de Dotation Agnes b
- Fondation Janssen Horizon
- AG2R La Mondiale
- Fondation Rothschild
- associations Odyssea and Prolific
- Region Ile-de-France
- Fondation pour la Recherche Medicale
- University Paris-Saclay, France
- Lundbeck Foundation [R215-2015-4081]
- Danish Cancer Society Research Council [KBVU-R146-A9322]
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Depletion of microtubule-associated protein ATIP3 reduces metaphase spindle length by interacting with Kif2A and its partner Dda3 in an Aurora kinase A-dependent manner. The absence of ATIP3 leads to the accumulation of Kif2A and Dda3 at spindle poles, affecting poleward microtubule flux and spindle shortening. ATIP3 maintains Aurora A activity on the poles to control Kif2A targeting and spindle size, highlighting their mutual regulation in controlling spindle length.
Maintaining the integrity of the mitotic spindle in metaphase is essential to ensure normal cell division. We show here that depletion of microtubule-associated protein ATIP3 reduces metaphase spindle length. Mass spectrometry analyses identified the microtubule minus-end depolymerizing kinesin Kif2A as an ATIP3 binding protein. We show that ATIP3 controls metaphase spindle length by interacting with Kif2A and its partner Dda3 in an Aurora kinase A-dependent manner. In the absence of ATIP3, Kif2A and Dda3 accumulate at spindle poles, which is consistent with reduced poleward microtubule flux and shortening of the spindle. ATIP3 silencing also limits Aurora A localization to the poles. Transfection of GFP-Aurora A, but not kinase-dead mutant, rescues the phenotype, indicating that ATIP3 maintains Aurora A activity on the poles to control Kif2A targeting and spindle size. Collectively, these data emphasize the pivotal role of Aurora kinase A and its mutual regulation with ATIP3 in controlling spindle length.
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