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

Cell Mol Life Sci. 2021 Feb;78(4):1765-1779. Epub 2020 Aug 13
Anne Nehlig 1 , Cynthia Seiler 1 , Yulia Steblyanko 2 , Florent Dingli 3 , Guillaume Arras 3 , Damarys Loew 3 , Julie Welburn 4 , Claude Prigent 5 , Marin Barisic 6 , Clara Nahmias 7
Anne Nehlig 1 , Cynthia Seiler 1 , Yulia Steblyanko 2 , Florent Dingli 3 , Guillaume Arras 3 , Damarys Loew 3 , Julie Welburn 4 , Claude Prigent 5 , Marin Barisic 6 , Clara Nahmias 7
+ et al

[No authors listed]

Author information
  • 1 Institut Gustave Roussy, Inserm, Biomarqueurs prédictifs et nouvelles stratégies thérapeutiques en oncologie, Université Paris-Saclay, 94800, Villejuif, France.
  • 2 Cell Division Laboratory, Danish Cancer Society Research Center, 2100, Copenhagen, Denmark.
  • 3 Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, Institut Curie, PSL Research University, 75248, Paris Cedex 05, France.
  • 4 Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, Scotland, UK.
  • 5 Institut de Génétique et Développement de Rennes (IGDR), Unité CNRS, UMR 6290, Université de Rennes, 35043, Rennes, France.
  • 6 Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
  • 7 Institut Gustave Roussy, Inserm, Biomarqueurs prédictifs et nouvelles stratégies thérapeutiques en oncologie, Université Paris-Saclay, 94800, Villejuif, France. clara.nahmias@inserm.fr.

摘要


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.

KEYWORDS: Aurora A, Dda3, Kif2A, MTUS1, Mitotic kinase, Mitotic spindle, Poleward microtubule flux