title: Alp7/TACC recruits kinesin-8-PP1 to the Ndc80 kinetochore protein for timely mitotic progression and chromosome movement.
abstract: Upon establishment of proper kinetochore-microtubule attachment, the spindle assembly checkpoint (SAC) must be silenced to allow onset of anaphase, which is when sister chromatids segregate equally to two daughter cells. However, how proper kinetochore-microtubule attachment leads to timely anaphase onset remains elusive. Furthermore, the molecular mechanisms of chromosome movement during anaphase A remain unclear. In this study, we show that the fission yeast Alp7/TACC protein recruits a protein complex consisting of the kinesin-8 (Klp5-Klp6) and protein phosphatase 1 (PP1) to the kinetochore upon kinetochore-microtubule attachment. Accumulation of this complex at the kinetochore, on the one hand, facilitates SAC inactivation through PP1, and, on the other hand, accelerates polewards chromosome movement driven by the Klp5-Klp6 motor. We identified an alp7 mutant that had specific defects in binding to the Klp5-Klp6-PP1 complex but with normal localisation to the microtubule and kinetochore. Consistent with our proposition, this mutant shows delayed anaphase onset and decelerated chromosome movement during anaphase A. We propose that the recruitment of kinesin-8-PP1 to the kinetochore through Alp7/TACC interaction plays a crucial role in regulation of timely mitotic progression and chromosome movement during anaphase A.
authors.affiliation: Laboratory of Cell Regulation, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK tnheok@gmail.com takashi.toda@cancer.org.uk.
authors.forename: Ngang Heok
authors.initials: NH
authors.lastname: Tang
authors.affiliation: Laboratory of Cell Regulation, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK tnheok@gmail.com takashi.toda@cancer.org.uk.
authors.forename: Takashi
authors.initials: T
authors.lastname: Toda
mesh_terms: D000705:Anaphase / Q000235:genetics*; D020090:Chromosome Segregation / Q000235:genetics; D016547:Kinesins / Q000235:genetics* / Q000378:metabolism; D018386:Kinetochores; D059566:M Phase Cell Cycle Checkpoints; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000235:genetics; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C479626:Alp7 protein, S pombe; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; C112472:NDC80 protein, S cerevisiae; C575627:NDC80 protein, S pombe; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D054645:Protein Phosphatase 1; C469734:Klp5 protein, S pombe; C459102:Klp6 protein, S pombe; D016547:Kinesins
keywords: Alp7/TACC; Anaphase A; Kinesin-8; Ndc80; Protein phosphatase I; Spindle assembly checkpoint/fission yeast