title: Girdin-mediated interactions between cadherin and the actin cytoskeleton are required for epithelial morphogenesis in Drosophila.
abstract: E-cadherin-mediated cell-cell adhesion is fundamental for epithelial tissue morphogenesis, physiology and repair. E-cadherin is a core transmembrane constituent of the zonula adherens (ZA), a belt-like adherens junction located at the apicolateral border in epithelial cells. The anchorage of ZA components to cortical actin filaments strengthens cell-cell cohesion and allows for junction contractility, which shapes epithelial tissues during development. Here, we report that the cytoskeletal adaptor protein Girdin physically and functionally interacts with components of the cadherin-catenin complex during Drosophila embryogenesis. Fly Girdin is broadly expressed throughout embryonic development and enriched at the ZA in epithelial tissues. Girdin associates with the cytoskeleton and co-precipitates with the cadherin-catenin complex protein α-Catenin (α-Cat). Girdin mutations strongly enhance adhesion defects associated with reduced DE-cadherin (DE-Cad) expression. Moreover, the fraction of DE-Cad molecules associated with the cytoskeleton decreases in the absence of Girdin, thereby identifying Girdin as a positive regulator of adherens junction function. Girdin mutant embryos display isolated epithelial cell cysts and rupture of the ventral midline, consistent with defects in cell-cell cohesion. In addition, loss of Girdin impairs the collective migration of epithelial cells, resulting in dorsal closure defects. We propose that Girdin stabilizes epithelial cell adhesion and promotes morphogenesis by regulating the linkage of the cadherin-catenin complex to the cytoskeleton.
authors.affiliation: Department of Molecular Biology, Medical Biochemistry and Pathology/Cancer Research Center, Laval University, and CRCHU-oncology axis, Québec, Québec, Canada G1R 3S3.
authors.forename: Elise
authors.initials: E
authors.lastname: Houssin
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada M5S 3G5.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Tepass
authors.affiliation: Department of Molecular Biology, Medical Biochemistry and Pathology/Cancer Research Center, Laval University, and CRCHU-oncology axis, Québec, Québec, Canada G1R 3S3 Patrick.Laprise@crchudequebec.ulaval.ca.
authors.forename: Patrick
authors.initials: P
authors.lastname: Laprise
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology
chemical_list: D000199:Actins; D015820:Cadherins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins
keywords: Armadillo; Cell-cell adhesion; Drosophila melanogaster; E-cadherin; Epithelial morphogenesis; Epithelial tissues; GIV; Girdin