Roles of Rho-associated kinase in cytokinesis; mutations in Rho- associated kinase phosphorylation sites impair cytokinetic segregation of glial filaments

Yoshihiro Yasui, Mutsuki Amano, Koh Ichi Nagata, Naoyuki Inagaki, Hideo Nakamura, Hideyuki Saya, Kozo Kaibuchi, Masaki Inagaki

Research output: Contribution to journalArticlepeer-review

145 Citations (Scopus)

Abstract

Rho-associated kinase (Rho-kinase), which is activated by the small GTPase Rho, regulates formation of stress fibers and focal adhesions, myosin fiber organization, and neurite retraction through the phosphorylation of cytoskeletal proteins, including myosin light chain, the ERM family proteins (ezrin, radixin, and moesin) and adducin. Rho-kinase was found to phosphorylate a type III intermediate filament (IF) protein, glial fibrillary acidic protein (GFAP), exclusively at the cleavage furrow during cytokinesis. In the present study, we examined the roles of Rho-kinase in cytokinesis, in particular organization of glial filaments during cytokinesis. Expression of the dominant-negative form of Rho-kinase inhibited the cytokinesis of Xenopus embryo and mammalian cells, the result being production of multinuclei. We then constructed a series of mutant GFAPs, where Rho-kinase phosphorylation sites were variously mutated, and expressed them in type III IF-negative cells. The mutations induced impaired segregation of glial filament (GFAP filament) into postmitotic daughter cells. As a result, an unusually long bridge-like cytoplasmic structure formed between the unseparated daughter cells. Alteration of other sites, including the cdc2 kinase phosphorylation site, led to no remarkable defect in glial filament separation. These results suggest that Rho-kinase is essential not only for actomyosin regulation but also for segregation of glial filaments into daughter cells which in turn ensures correct cytokinetic processes.

Original languageEnglish
Pages (from-to)1249-1258
Number of pages10
JournalJournal of Cell Biology
Volume143
Issue number5
DOIs
Publication statusPublished - 30-11-1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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