Cell cycle-associated changes in Slingshot phosphatase activity and roles in cytokinesis in animal cells

Noriko Kaji, Kazumasa Ohashi, Mika Shuin, Ryusuke Niwa, Tadashi Uemura, Kensaku Mizuno

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

Abstract

During cytokinesis the actomyosin-based contractile ring is formed at the equator, constricted, and then dis-assembled prior to cell abscission. Cofilin stimulates actin filament disassembly and is implicated in the regulation of contractile ring dynamics. However, little is known about the mechanism controlling cofilin activity during cytokinesis. Cofilin is inactivated by phosphorylation on Ser-3 by LIM-kinase-1 (LIMK1) and is reactivated by a protein phosphatase Slingshot-1 (SSH1). Here we show that the phosphatase activity of SSH1 decreases in the early stages of mitosis and is elevated in telophase and cytokinesis in HeLa cells, a time course correlating with that of cofilin dephosphorylation. SSH1 co-localizes with F-actin and accumulates onto the cleavage furrow and the midbody. Expression of a phosphatase-inactive SSH1 induces aberrant accumulation of F-actin and phospho-cofilin near the midbody in the final stage of cytokinesis and frequently leads to the regression of the cleavage furrow and the formation of multinucleate cells. Co-expression of cofilin rescued the inhibitory effect of phosphatase-inactive SSH1 on cytokinesis. These results suggest that SSH1 plays a critical role in cytokinesis by dephosphorylating and reactivating cofilin in later stages of mitosis.

Original languageEnglish
Pages (from-to)33450-33455
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number35
DOIs
Publication statusPublished - 2003 Aug 29

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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