title: Kinetochore-localized PP1-Sds22 couples chromosome segregation to polar relaxation.
abstract: Cell division requires the precise coordination of chromosome segregation and cytokinesis. This coordination is achieved by the recruitment of an actomyosin regulator, Ect2, to overlapping microtubules at the centre of the elongating anaphase spindle. Ect2 then signals to the overlying cortex to promote the assembly and constriction of an actomyosin ring between segregating chromosomes. Here, by studying division in proliferating Drosophila and human cells, we demonstrate the existence of a second, parallel signalling pathway, which triggers the relaxation of the polar cell cortex at mid anaphase. This is independent of furrow formation, centrosomes and microtubules and, instead, depends on PP1 phosphatase and its regulatory subunit Sds22 (refs 2, 3). As separating chromosomes move towards the polar cortex at mid anaphase, kinetochore-localized PP1-Sds22 helps to break cortical symmetry by inducing the dephosphorylation and inactivation of ezrin/radixin/moesin proteins at cell poles. This promotes local softening of the cortex, facilitating anaphase elongation and orderly cell division. In summary, this identifies a conserved kinetochore-based phosphatase signal and substrate, which function together to link anaphase chromosome movements to cortical polarization, thereby coupling chromosome segregation to cell division.
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Nelio T L
authors.initials: NT
authors.lastname: Rodrigues
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Sergey
authors.initials: S
authors.lastname: Lekomtsev
authors.affiliation: Sainte-Justine Hospital Research Center, Montréal, Québec H3T 1C5, Canada.
authors.forename: Silvana
authors.initials: S
authors.lastname: Jananji
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Janos
authors.initials: J
authors.lastname: Kriston-Vizi
authors.affiliation: Sainte-Justine Hospital Research Center, Montréal, Québec H3T 1C5, Canada.|Department of Pathology and Cell Biology, Université de Montréal, Montréal, Québec H3T 1J4, Canada.
authors.forename: Gilles R X
authors.initials: GR
authors.lastname: Hickson
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK.|Institute for the Physics of Living Systems, University College London, Gower Street, London WC1E 6BT, UK.|CelTisPhyBio Labex, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: Buzz
authors.initials: B
authors.lastname: Baum
mesh_terms: D000199:Actins / Q000378:metabolism; D000705:Anaphase; D000818:Animals; D016764:Cell Polarity; D018385:Centrosome / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D020090:Chromosome Segregation; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D018386:Kinetochores / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D015398:Signal Transduction; D000099149:Ezrin
chemical_list: D000199:Actins; D002843:Chromatin; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D054645:Protein Phosphatase 1; D000099149:Ezrin; C509751:PPP1R7 protein, human; C071058:moesin; C071776:radixin