title: Cdk1 Activates Pre-mitotic Nuclear Envelope Dynein Recruitment and Apical Nuclear Migration in Neural Stem Cells.
abstract: Dynein recruitment to the nuclear envelope is required for pre-mitotic nucleus-centrosome interactions in nonneuronal cells and for apical nuclear migration in neural stem cells. In each case, dynein is recruited to the nuclear envelope (NE) specifically during G2 via two nuclear pore-mediated mechanisms involving RanBP2-BicD2 and Nup133-CENP-F. The mechanisms responsible for cell-cycle control of this behavior are unknown. We now find that Cdk1 serves as a direct master controller for NE dynein recruitment in neural stem cells and HeLa cells. Cdk1 phosphorylates conserved sites within RanBP2 and activates BicD2 binding and early dynein recruitment. Late recruitment is triggered by a Cdk1-induced export of CENP-F from the nucleus. Forced NE targeting of BicD2 overrides Cdk1 inhibition, fully rescuing dynein recruitment and nuclear migration in neural stem cells. These results reveal how NE dynein recruitment is cell-cycle regulated and identify the trigger mechanism for apical nuclear migration in the brain.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA. Electronic address: adb2160@cumc.columbia.edu.
authors.forename: Alexandre D
authors.initials: AD
authors.lastname: Baffet
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hu
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA. Electronic address: rv2025@cumc.columbia.edu.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Vallee
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis; D008959:Models, Neurological; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D055647:Rats, Transgenic
chemical_list: C584496:Bicd2 protein, rat; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; D034741:RNA, Small Interfering; C094493:ran-binding protein 2; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; C548796:Cdk1 protein, rat; D018844:Cyclin-Dependent Kinases; D004398:Dyneins