Koehler Katrin

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The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation

2015-08-05 , Carvalhal, Sara , Ribeiro, Susana Abreu , Arocena, Miguel , Kasciukovic, Taciana , Temme, Achim , Koehler, Katrin , Huebner, Angela , Griffis, Eric R.

The formation of the mitotic spindle is a complex process that requires massive cellular reorganization. Regulation by mitotic kinases controls this entire process. One of these mitotic controllers is Aurora A kinase, which is itself highly regulated. In this study, we show that the nuclear pore protein ALADIN is a novel spatial regulator of Aurora A. Without ALADIN, Aurora A spreads from centrosomes onto spindle microtubules, which affects the distribution of a subset of microtubule regulators and slows spindle assembly and chromosome alignment. ALADIN interacts with inactive Aurora A and is recruited to the spindle pole after Aurora A inhibition. Of interest, mutations in ALADIN cause triple A syndrome. We find that some of the mitotic phenotypes that we observe after ALADIN depletion also occur in cells from triple A syndrome patients, which raises the possibility that mitotic errors may underlie part of the etiology of this syndrome.