title: The kinesin-14 Klp2 is negatively regulated by the SIN for proper spindle elongation and telophase nuclear positioning.
abstract: In Schizosaccharomyces pombe, a late mitotic kinase pathway called the septation initiation network (SIN) triggers cytokinesis. Here we show that the SIN is also involved in regulating anaphase spindle elongation and telophase nuclear positioning via inhibition of Klp2, a minus end-directed kinesin-14. Klp2 is known to localize to microtubules (MTs) and have roles in interphase nuclear positioning, mitotic chromosome alignment, and nuclear migration during karyogamy (nuclear fusion during mating). We observe SIN-dependent disappearance of Klp2 from MTs in anaphase, and we find that this is mediated by direct phosphorylation of Klp2 by the SIN kinase Sid2, which abrogates loading of Klp2 onto MTs by inhibiting its interaction with Mal3 (EB1 homologue). Disruption of Klp2 MT localization is required for efficient anaphase spindle elongation. Furthermore, when cytokinesis is delayed, SIN inhibition of Klp2 acts in concert with microtubules emanating from the equatorial microtubule-organizing center to position the nuclei away from the cell division site. These results reveal novel functions of the SIN in regulating the MT cytoskeleton and suggest that the SIN may have broader functions in regulating cellular organization in late mitosis than previously realized.
authors.affiliation: Department of Microbiology and Physiological Systems and Program in Cell Dynamics, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mana-Capelli
authors.forename: Janel R
authors.initials: JR
authors.lastname: McLean
authors.forename: Chun-Ti
authors.initials: CT
authors.lastname: Chen
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Gould
authors.forename: Dannel
authors.initials: D
authors.lastname: McCollum
mesh_terms: D000705:Anaphase / Q000235:genetics; D048749:Cytokinesis / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D022101:Microtubule-Organizing Center / Q000378:metabolism; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000235:genetics; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D013692:Telophase / Q000235:genetics
chemical_list: C502171:Klp2 protein, S pombe; C108851:Mal3 protein, S pombe; D008869:Microtubule-Associated Proteins; D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; C113816:Sid2 protein, S pombe