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Article Dans Une Revue Cellular and Molecular Life Sciences Année : 2021

Reciprocal regulation of Aurora kinase A and ATIP3 in the control of metaphase spindle length

Résumé

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 identi-ied 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 lux 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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Dates et versions

hal-02924786 , version 1 (31-08-2020)

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Anne Nehlig, Cynthia Seiler, Yulia Steblyanko, Florent Dingli, Guillaume Arras, et al.. Reciprocal regulation of Aurora kinase A and ATIP3 in the control of metaphase spindle length. Cellular and Molecular Life Sciences, 2021, 78 (4), pp.1765-1779. ⟨10.1007/s00018-020-03614-8⟩. ⟨hal-02924786⟩
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