title: Cell cycle regulation of microtubule interactomes: multi-layered regulation is critical for the interphase/mitosis transition.
abstract: Microtubules dramatically change their dynamics and organization at the entry into mitosis. Although this change is mediated by microtubule-associated proteins (MAPs), how MAPs themselves are regulated is not well understood. Here we used an integrated multi-level approach to establish the framework and biological significance of MAP regulation critical for the interphase/mitosis transition. Firstly, we applied quantitative proteomics to determine global cell cycle changes in the profiles of MAPs in human and Drosophila cells. This uncovered a wide range of cell cycle regulations of MAPs previously unidentified. Secondly, systematic studies of human kinesins highlighted an overlooked aspect of kinesins: most mitotic kinesins suppress their affinity to microtubules or reduce their protein levels in interphase in combination with nuclear localization. Thirdly, in-depth analysis of a novel Drosophila MAP (Mink) revealed that the suppression of the microtubule affinity of this mitotic MAP in combination with nuclear localization is essential for microtubule organization in interphase, and phosphorylation of Mink is needed for kinetochore-microtubule attachment in mitosis. Thus, this first comprehensive analysis of MAP regulation for the interphase/mitosis transition advances our understanding of kinesin biology and reveals the prevalence and importance of multi-layered MAP regulation.
authors.affiliation: Wellcome Trust Centre for Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh EH9 3JR, United Kingdom.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Syred
authors.forename: Julie
authors.initials: J
authors.lastname: Welburn
authors.forename: Juri
authors.initials: J
authors.lastname: Rappsilber
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohkura
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D059447:Cell Cycle Checkpoints / Q000502:physiology*; D002460:Cell Line; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007399:Interphase / Q000502:physiology; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D040901:Proteomics; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D029721:Drosophila Proteins; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; D016547:Kinesins
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