title: The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation.
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.
authors.affiliation: Centre for Gene Regulation and Expression, University of Dundee, College of Life Sciences, Dundee DD1 5EH, United Kingdom.
authors.forename: Sara
authors.initials: S
authors.lastname: Carvalhal
authors.affiliation: Physiology Course, Marine Biological Laboratory, Woods Hole, MA 02543 Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom.
authors.forename: Susana Abreu
authors.initials: SA
authors.lastname: Ribeiro
authors.affiliation: Centre for Gene Regulation and Expression, University of Dundee, College of Life Sciences, Dundee DD1 5EH, United Kingdom.
authors.forename: Miguel
authors.initials: M
authors.lastname: Arocena
authors.affiliation: Centre for Gene Regulation and Expression, University of Dundee, College of Life Sciences, Dundee DD1 5EH, United Kingdom.
authors.forename: Taciana
authors.initials: T
authors.lastname: Kasciukovic
authors.affiliation: Department of Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Temme
authors.affiliation: Department of Paediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Koehler
authors.affiliation: Department of Paediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Huebner
authors.affiliation: Centre for Gene Regulation and Expression, University of Dundee, College of Life Sciences, Dundee DD1 5EH, United Kingdom Physiology Course, Marine Biological Laboratory, Woods Hole, MA 02543 e.griffis@dundee.ac.uk.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Griffis
mesh_terms: D000309:Adrenal Insufficiency / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D064096:Aurora Kinase A / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D004331:Drosophila melanogaster; D004931:Esophageal Achalasia / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D011485:Protein Binding; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: C416506:AAAS protein, human; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; C576917:AURKA protein, human; D064096:Aurora Kinase A