title: Involvement of afadin in barrier function and homeostasis of mouse intestinal epithelia.
abstract: Afadin interacts with the cytoplasmic region of nectins, which are immunoglobulin-like cell adhesion molecules at adherens junctions, and links them to the actin cytoskeleton. Afadin regulates activities of cells in culture such as directional motility, proliferation and survival. We used Cre-loxP technology to generate mice conditionally lacking afadin specifically in the intestinal epithelia after birth. The loss of afadin caused increased paracellular permeability in the intestinal mucosa and enhanced susceptibility to the tissue destruction induced by dextran sulfate sodium. The junctional architecture of the intestinal epithelia appeared to be preserved, whereas the deficiency of afadin caused the mislocalization of nectin-2 and nectin-3 from adherens junctions to basolateral membrane domains but not that of other components of apical junctions. By contrast, such phenotypic changes were undetected in mice lacking nectin-2, nectin-3 or both. These findings suggest that afadin plays crucial roles, independently of the role as the nectin-afadin module, in barrier function and homeostasis of the intestinal epithelia once the epithelial structure has been established.
authors.affiliation: Department of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Tanaka-Okamoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Hori
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ishizaki
authors.forename: Yu
authors.initials: Y
authors.lastname: Itoh
authors.forename: Sachiko
authors.initials: S
authors.lastname: Onishi
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
authors.forename: Jun
authors.initials: J
authors.lastname: Miyoshi
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016264:Dextran Sulfate / Q000494:pharmacology; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000378:metabolism*; D000075983:Nectins; D010539:Permeability; D010641:Phenotype
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C000619017:Nectin3 protein, mouse; D000075983:Nectins; C108835:afadin; D016264:Dextran Sulfate