論文

査読有り
2017年10月

Mib1 contributes to persistent directional cell migration by regulating the Ctnnd1-Rac1 pathway

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Takamasa Mizoguchi
  • ,
  • Shoko lkeda
  • ,
  • Saori Watanabe
  • ,
  • Michiko Sugawara
  • ,
  • Motoyuki Itoh

114
44
開始ページ
E9280
終了ページ
E9289
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.1712560114
出版者・発行元
NATL ACAD SCIENCES

Persistent directional cell migration is involved in animal development and diseases. The small GTPase Rac1 is involved in F-actin and focal adhesion dynamics. Local Rac1 activity is required for persistent directional migration, whereas global, hyperactivated Rac1 enhances random cell migration. Therefore, precise control of Rac1 activity is important for proper directional cell migration. However, the molecular mechanism underlying the regulation of Rac1 activity in persistent directional cell migration is not fully understood. Here, we show that the ubiquitin ligase mind bomb 1 (Mib1) is involved in persistent directional cell migration. We found that knockdown of MIB1 led to an increase in random cell migration in HeLa cells in a wound-closure assay. Furthermore, we explored novel Mib1 substrates for cell migration and found that Mib1 ubiquitinates Ctnnd1. Mib1-mediated ubiq-uitination of Ctnnd1 K547 attenuated Rac1 activation in cultured cells. In addition, we found that posterior lateral line primordium cells in the zebrafish mib1(ta52b) mutant showed increased random migration and loss of directional F-actin-based protrusion formation. Knock down of Ctnnd1 partially rescued posterior lateral line primordium cell migration defects in the mib1(ta52b) mutant. Taken together, our data suggest that Mib1 plays an important role in cell migration and that persistent directional cell migration is regulated, at least in part, by the Mib1-Ctnnd1-Rac1 pathway.

Web of Science ® 被引用回数 : 12

リンク情報
DOI
https://doi.org/10.1073/pnas.1712560114
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000414127400015&DestApp=WOS_CPL
URL
http://orcid.org/0000-0002-9475-6495

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