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Thrombomodulin is an ezrin‐interacting protein that controls epithelial morphology and promotes collective cell migration
Author(s) -
Hsu YunYan,
Shi GueyYueh,
Kuo ChengHsiang,
Liu ShuLin,
Wu ChingMing,
Ma ChihYuan,
Lin FengYi,
Yang HsiYuan,
Wu HuaLin
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-204917
Subject(s) - ezrin , microbiology and biotechnology , cell migration , thrombomodulin , cytoplasm , cell adhesion , cell , chemistry , epidermal growth factor , biology , cytoskeleton , cell culture , immunology , biochemistry , thrombin , platelet , genetics
Adhesive interactions between cells are needed to maintain tissue architecture during development, tissue renewal and wound healing. Thrombo‐modulin (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 522 RKK 524 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.—Hsu, Y.‐Y., Shi, G.‐Y., Kuo, C.‐H., Liu, S.‐L., Wu, C.‐M., Ma, C.‐Y., Lin, F.‐Y., Yang, H.‐Y., Wu, H.‐L. Thrombomodulin is an ezrin‐interacting protein that controls epithelial morphology and promotes collective cell migration. FASEB J. 26, 3440–3452 (2012). www.fasebj.org