Thrombomodulin is an ezrin-interacting protein that controls epithelial morphology and promotes collective cell migration

Yun Yan Hsu, Guey Yueh Shi, Cheng Hsiang Kuo, Shu Lin Liu, Ching Ming Wu, Chih Yuan Ma, Feng Yi Lin, Hsi Yuan Yang, Hua Lin Wu

研究成果: Article同行評審

32 引文 斯高帕斯(Scopus)

摘要

Adhesive interactions between cells are needed to maintain tissue architecture during development, tissue renewal and wound healing. Thrombomodulin (TM) is an integral membrane protein that participates in cell-cell adhesion through its extracellular lectin-like domain. However, the molecular basis of TM-mediated cell-cell adhesion is poorly understood. Here, we demonstrate that TM is linked to the actin cytoskeleton via ezrin. In vitro binding assays showed that the TM cytoplasmic domain bound directly to the N-terminal domain of ezrin. Mutational analysis of the TM cytoplasmic domain identified 522RKK524 as important ezrin-binding residues. In epidermal epithelial A431 cells, TM colocalized with ezrin and actin filaments at cell-cell contacts. Knockdown of endogenous TM expression by RNA interference induced morphological changes and accelerated cell migration in A431 cells. Moreover, epidermal growth factor, upstream of ezrin activation, stimulated the interaction between ezrin and TM. In skin wound healing of mice, TM and ezrin were highly expressed in neoepidermis, implying that both proteins are key molecules in reepithelialization that requires collective cell migration of epithelial cells. Finally, exogenous expression of TM in TM-deficient melanoma A2058 cells promoted collective cell migration. In summary, TM, which associates with ezrin and actin filaments, maintains epithelial morphology and promotes collective cell migration.

原文English
頁(從 - 到)3440-3452
頁數13
期刊FASEB Journal
26
發行號8
DOIs
出版狀態Published - 2012 八月

All Science Journal Classification (ASJC) codes

  • 生物技術
  • 生物化學
  • 分子生物學
  • 遺傳學

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