title: Genetic ablation of afadin causes mislocalization and deformation of Paneth cells in the mouse small intestinal epithelium.
abstract: Afadin is an actin filament-binding protein that acts cooperatively in cell adhesion with the cell adhesion molecule nectin, and in directional cell movement with the small G protein Rap1 in a nectin-independent manner. We studied the role of afadin in the organization of the small intestinal epithelium using afadin conditional gene knockout (cKO) mice. Afadin was localized at adherens junctions of all types of epithelial cells throughout the crypt-villus axis. Paneth cells were localized at the base of the crypt in control mice, but not confined there, and migrated into the villi in afadin-cKO mice. The distribution of other types of epithelial cells did not change significantly in the mutant mice. The Paneth cells remaining in the crypt exhibited abnormal shapes, were buried between adjacent cells, and did not face the lumen. In these cells, the formation of adherens junctions and tight junctions was impaired. Rap1 and EphB3 were highly expressed in control Paneth cells but markedly down-regulated in the afadin-deficient Paneth cells. Taken together, the results indicate that afadin plays a role in the restricted localization of Paneth cells at the base of the crypt by maintaining their adhesion to adjacent crypt cells and inhibiting their movement toward the top of villi.
authors.affiliation: Department of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan; Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Tanaka-Okamoto
authors.affiliation: Department of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan; Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Department of Molecular Biology, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Miyoshi
authors.affiliation: Department of Neural Regeneration and Cell Communication, Mie University Graduate School of Medicine, Mie, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Mizoguchi
authors.affiliation: Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Mizutani
authors.affiliation: Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
authors.affiliation: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D015536:Down-Regulation; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D019879:Paneth Cells / Q000166:cytology* / Q000378:metabolism*; D036223:Receptor, EphB3 / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism / Q000473:pathology; D020827:rap1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008840:Microfilament Proteins; C108835:afadin; D036223:Receptor, EphB3; D020827:rap1 GTP-Binding Proteins