title: Importin β2 Mediates the Spatio-temporal Regulation of Anillin through a Noncanonical Nuclear Localization Signal.
abstract: The compartmentalization of cell cycle regulators is a common mechanism to ensure the precise temporal control of key cell cycle events. For instance, many mitotic spindle assembly factors are known to be sequestered in the nucleus prior to mitotic onset. Similarly, the essential cytokinetic factor anillin, which functions at the cell membrane to promote the physical separation of daughter cells at the end of mitosis, is sequestered in the nucleus during interphase. To address the mechanism and role of anillin targeting to the nucleus in interphase, we identified the nuclear targeting motif. Here, we show that anillin is targeted to the nucleus by importin β2 in a Ran-dependent manner through an atypical basic patch PY nuclear localization signal motif. We show that although importin β2 binding does not regulate anillin's function in mitosis, it is required to prevent the cytosolic accumulation of anillin, which disrupts cellular architecture during interphase. The nuclear sequestration of anillin during interphase serves to restrict anillin's function at the cell membrane to mitosis and allows anillin to be rapidly available when the nuclear envelope breaks down to remodel the cellular architecture necessary for successful cell division.
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Anan
authors.initials: A
authors.lastname: Chen
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Tara K
authors.initials: TK
authors.lastname: Akhshi
authors.affiliation: Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Brigitte D
authors.initials: BD
authors.lastname: Lavoie
authors.affiliation: From the Departments of Biochemistry and Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada andrew.wilde@utoronto.ca.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wilde
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics*; D048749:Cytokinesis / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D007399:Interphase / Q000502:physiology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D009685:Nuclear Envelope / Q000378:metabolism; D019913:Nuclear Localization Signals; D021381:Protein Transport; D028961:beta Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000591059:ANLN protein, human; D008840:Microfilament Proteins; D019913:Nuclear Localization Signals; C108121:TNPO1 protein, human; D028961:beta Karyopherins
keywords: cell cycle; cell division; nuclear transport; nucleus; protein targeting
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