title: Binding between the junctional proteins afadin and PLEKHA7 and implication in the formation of adherens junction in epithelial cells.
abstract: Adherens junction (AJ) is a specialized cell-cell junction structure that plays a role in mechanically connecting adjacent cells to resist strong contractile forces and to maintain tissue structure, particularly in the epithelium. AJ is mainly comprised of cell adhesion molecules cadherin and nectin and their associating cytoplasmic proteins including β-catenin, α-catenin, p120(ctn), and afadin. Our series of studies have revealed that nectin first forms cell-cell adhesion and then recruits cadherin to form AJ. The recruitment of cadherin by nectin is mediated by the binding of α-catenin and p120(ctn) to afadin. Recent studies showed that PLEKHA7 binds to p120(ctn), which is associated with E-cadherin, and maintains the integrity of AJ in epithelial cells. In this study, we showed that PLEKHA7 bound to afadin in addition to p120(ctn) and was recruited to the nectin-3α-based cell-cell adhesion site in a manner dependent on afadin, but not on p120(ctn). The binding of PLEKHA7 to afadin was required for the proper formation of AJ, but not for the formation of tight junction, in EpH4 mouse mammary gland epithelial cells. These results indicate that PLEKHA7 plays a cooperative role with nectin and afadin in the proper formation of AJ in epithelial cells.
authors.affiliation: From the Division of Molecular and Cellular Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Kurita
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamada
authors.forename: Etsuko
authors.initials: E
authors.lastname: Rikitsu
authors.forename: Wataru
authors.initials: W
authors.lastname: Ikeda
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007739:L Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D000075983:Nectins; D034622:RNA Interference; D019108:Tight Junctions / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D002352:Carrier Proteins; D051177:Catenins; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D000075983:Nectins; C584830:PLEKHA7 protein, mouse; C108835:afadin; D000095002:Delta Catenin
keywords: Adherens Junction; Afadin; Cadherins; Cell Adhesion; Epithelial Cell; Nectin; PLEKHA7; Protein-Protein Interactions