title: TOR complex 2 localises to the cytokinetic actomyosin ring and controls the fidelity of cytokinesis.
abstract: The timing of cell division is controlled by the coupled regulation of growth and division. The target of rapamycin (TOR) signalling network synchronises these processes with the environmental setting. Here, we describe a novel interaction of the fission yeast TOR complex 2 (TORC2) with the cytokinetic actomyosin ring (CAR), and a novel role for TORC2 in regulating the timing and fidelity of cytokinesis. Disruption of TORC2 or its localisation results in defects in CAR morphology and constriction. We provide evidence that the myosin II protein Myp2 and the myosin V protein Myo51 play roles in recruiting TORC2 to the CAR. We show that Myp2 and TORC2 are co-dependent upon each other for their normal localisation to the cytokinetic machinery. We go on to show that TORC2-dependent phosphorylation of actin-capping protein 1 (Acp1, a known regulator of cytokinesis) controls CAR stability, modulates Acp1-Acp2 (the equivalent of the mammalian CAPZA-CAPZB) heterodimer formation and is essential for survival upon stress. Thus, TORC2 localisation to the CAR, and TORC2-dependent Acp1 phosphorylation contributes to timely control and the fidelity of cytokinesis and cell division.
authors.affiliation: School of Biosciences, University of Kent, Giles Lane, Canterbury, Kent CT2 7NJ, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Baker
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Kirkham
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Lenka
authors.initials: L
authors.lastname: Halova
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Atkin
authors.affiliation: Proteome Center Tübingen, Auf der Morgenstelle 15, Tübingen 72076, Germany.
authors.forename: Mirita
authors.initials: M
authors.lastname: Franz-Wachtel
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: David
authors.initials: D
authors.lastname: Cobley
authors.affiliation: Proteome Center Tübingen, Auf der Morgenstelle 15, Tübingen 72076, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Krug
authors.affiliation: Proteome Center Tübingen, Auf der Morgenstelle 15, Tübingen 72076, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Maček
authors.affiliation: School of Biosciences, University of Kent, Giles Lane, Canterbury, Kent CT2 7NJ, UK d.p.mulvihill@kent.ac.uk Janni.Petersen@Flinders.edu.au.
authors.forename: Daniel P
authors.identifier: 0000-0003-2502-5274
authors.initials: DP
authors.lastname: Mulvihill
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK Flinders Centre for Innovation in Cancer, School of Medicine, Flinders University, Adelaide, SA 5001, Australia South Australia Health and Medical Research Institute, North Terrace, PO Box 11060, Adelaide, SA 5000, Australia d.p.mulvihill@kent.ac.uk Janni.Petersen@Flinders.edu.au.
authors.forename: Janni
authors.initials: J
authors.lastname: Petersen
mesh_terms: D051344:Actin Capping Proteins / Q000235:genetics* / Q000378:metabolism; D000199:Actins / Q000235:genetics; D000205:Actomyosin / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D048749:Cytokinesis / Q000235:genetics*; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000235:genetics* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D009218:Myosins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D012568:Schizosaccharomyces / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D051344:Actin Capping Proteins; D000199:Actins; D046912:Multiprotein Complexes; C110514:Myp2 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D000205:Actomyosin; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases; C554096:Myo51 protein, S pombe; D018995:Myosin Heavy Chains; D009218:Myosins
keywords: Acp1; CAPZA; Myosin II; Myosin V; Rictor; Schizosaccharomyces pombe; TOR; TORC2