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

Mol Biol Cell. 2015 Oct 1;26(19):3424-38. doi: 10.1091/mbc.E15-02-0113. Epub 2015 Aug 5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Insufficiency / enzymology
  • Adrenal Insufficiency / metabolism
  • Animals
  • Aurora Kinase A / metabolism*
  • Cell Cycle / physiology
  • Cells, Cultured
  • Drosophila melanogaster
  • Esophageal Achalasia / enzymology
  • Esophageal Achalasia / metabolism
  • Humans
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism
  • Mitosis / physiology
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Pore Complex Proteins / metabolism*
  • Protein Binding
  • Spindle Apparatus / metabolism*

Substances

  • AAAS protein, human
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Nuclear Pore Complex Proteins
  • AURKA protein, human
  • Aurora Kinase A

Supplementary concepts

  • Achalasia Addisonianism Alacrimia syndrome