RRC ID 66030
著者 Mizoguchi T, Ikeda S, Watanabe S, Sugawara M, Itoh M.
タイトル Mib1 contributes to persistent directional cell migration by regulating the Ctnnd1-Rac1 pathway.
ジャーナル Proc Natl Acad Sci U S A
Abstract 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 ubiquitination of Ctnnd1 K547 attenuated Rac1 activation in cultured cells. In addition, we found that posterior lateral line primordium cells in the zebrafish mib1ta52b mutant showed increased random migration and loss of directional F-actin-based protrusion formation. Knockdown of Ctnnd1 partially rescued posterior lateral line primordium cell migration defects in the mib1ta52b 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.
巻・号 114(44)
ページ E9280-E9289
公開日 2017-10-31
DOI 10.1073/pnas.1712560114
PII 1712560114
PMID 29078376
PMC PMC5676927
MeSH Actins / metabolism Animals Cell Adhesion / physiology Cell Line, Tumor Cell Movement / physiology* Focal Adhesions / metabolism Focal Adhesions / physiology HeLa Cells Humans Signal Transduction / physiology* Ubiquitin-Protein Ligases / metabolism* Ubiquitination / physiology Zebrafish / metabolism Zebrafish / physiology rac1 GTP-Binding Protein / metabolism*
IF 9.412
リソース情報
ゼブラフィッシュ hspGFF15A  Tg(UAS:GFP)