4.8 Article

Kinetochore-localized PP1-Sds22 couples chromosome segregation to polar relaxation

Journal

NATURE
Volume 524, Issue 7566, Pages 489-+

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nature14496

Keywords

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Funding

  1. Cancer Research UK
  2. Medical Research Council
  3. Canadian Institutes of Health Research
  4. Canada Foundation for Innovation
  5. Fonds de Recherche du Quebec-Sante
  6. Cole Foundation
  7. INCa
  8. BBSRC [BB/K009001/1]
  9. Biotechnology and Biological Sciences Research Council [BB/K009001/1] Funding Source: researchfish
  10. Cancer Research UK [17343, 9786] Funding Source: researchfish
  11. Medical Research Council [MC_CF12266] Funding Source: researchfish
  12. BBSRC [BB/K009001/1] Funding Source: UKRI

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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(1). Ect2 then signals to the overlying cortex to promote the assembly and constriction of an actomyosin ring between segregating chromosomes(1). 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(2,3), 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.

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