title: Direct interaction of 14-3-3ζ with ezrin promotes cell migration by regulating the formation of membrane ruffle.
abstract: 14-3-3 proteins have been shown to regulate the actin cytoskeleton remodeling, cell adhesion and migration. In this study, we identified ezrin, a cross-linker between plasma membrane and actin cytoskeleton, as a novel 14-3-3ζ interacting partner. The direct interaction between 14-3-3ζ and ezrin was validated in the cells and by in vitro assays. We showed that the 14-3-3ζ binding region in ezrin was located within the N-terminal and central α-helical domains and that the αG-to-αI helices of 14-3-3ζ are responsible for the binding to ezrin. Functional analyses revealed that the regulation of cell migration and membrane ruffling by 14-3-3ζ is ezrin dependent, for which the integrity of ezrin protein was required. Conversely, the knockdown of 14-3-3ζ abrogates also the stimulatory effect of ezrin on cell migration and membrane ruffling. Moreover, we found that the phosphorylation of Thr567 in ezrin facilitates the 14-3-3ζ-ezrin interaction and the formation of membrane ruffles. Taken together, these results suggest strongly that the functions of these two proteins in cell migration are linked and might be mediated by their direct physical interaction, which is important for the formation of membrane ruffles.
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Miaojuan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Liu
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Xuejuan
authors.initials: X
authors.lastname: Gao
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Cuihua
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: He
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education, Institute of Life and Health Engineering, Jinan University, Guangzhou 510632, China.. Electronic address: langxialiu@gmail.com.
authors.forename: Langxia
authors.initials: L
authors.lastname: Liu
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000473:pathology*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins; D000099149:Ezrin
chemical_list: D048948:14-3-3 Proteins; D000911:Antibodies, Monoclonal; D003598:Cytoskeletal Proteins; D011994:Recombinant Proteins; D000099149:Ezrin
keywords: 14-3-3 zeta; actin cytoskeleton remodeling; cell migration; ezrin; protein–protein interaction