Hippo pathway regulation by cell morphology and stress fibers

Ken Ichi Wada, Kazuyoshi Itoga, Teruo Okano, Shigenobu Yonemura, Hiroshi Sasaki

研究成果: Contribution to journalArticle査読

521 被引用数 (Scopus)

抄録

The Hippo signaling pathway plays an important role in regulation of cell proliferation. Cell density regulates the Hippo pathway in cultured cells; however, the mechanism by which cells detect density remains unclear. In this study, we demonstrated that changes in cell morphology are a key factor. Morphological manipulation of single cells without cell-cell contact resulted in flat spread or round compact cells with nuclear or cytoplasmic Yap, respectively. Stress fibers increased in response to expanded cell areas, and F-actin regulated Yap downstream of cell morphology. Cell morphology- and F-actin-regulated phosphorylation of Yap, and the effects of F-actin were suppressed by modulation of Lats. Our results suggest that cell morphology is an important factor in the regulation of the Hippo pathway, which is mediated by stress fibers consisting of F-actin acting upstream of, or on Lats, and that cells can detect density through their resulting morphology. This cell morphology (stress-fiber)-mediated mechanism probably cooperates with a cell-cell contact (adhesion)-mediated mechanism involving the Hippo pathway to achieve density-dependent control of cell proliferation.

本文言語英語
ページ(範囲)3907-3914
ページ数8
ジャーナルDevelopment
138
18
DOI
出版ステータス出版済み - 9 15 2011
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 発生生物学

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