title: Role of integrins in the assembly and function of hensin in intercalated cells.
abstract: Epithelial differentiation proceeds in at least two steps: Conversion of a nonepithelial cell into an epithelial sheet followed by terminal differentiation into the mature epithelial phenotype. It was recently discovered that the extracellular matrix (ECM) protein hensin is able to convert a renal intercalated cell line from a flat, squamous shape into a cuboidal or columnar epithelium. Global knockout of hensin in mice results in embryonic lethality at the time that the first columnar cells appear. Here, antibodies that either activate or block integrin beta1 were used to demonstrate that activation of integrin alpha v beta 1 causes deposition of hensin in the ECM. Once hensin polymerizes and deposits into the ECM, it binds to integrin alpha 6 and mediates the conversion of epithelial cells to a cuboidal phenotype capable of apical endocytosis; therefore, multiple integrins play a role in the terminal differentiation of the intercalated cell: alpha v beta 1 generates polymerized hensin, and another set of integrins (containing alpha 6) mediates signals between hensin and the interior of the cells.
authors.affiliation: Pediatric Nephrology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 777, Rochester, NY 14642, USA. soundarapandian_vijayakumar@urmc.rochester.edu
authors.forename: Soundarapandian
authors.initials: S
authors.lastname: Vijayakumar
authors.forename: Hediye
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: Paul
authors.initials: P
authors.lastname: Tempst
authors.forename: Qais
authors.initials: Q
authors.lastname: Al-Awqati
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D004847:Epithelial Cells / Q000166:cytology*; D016023:Integrins / Q000502:physiology*; D007668:Kidney / Q000166:cytology*; D051379:Mice; D009077:Mucins / Q000502:physiology*; D025521:Tumor Suppressor Proteins
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C114202:Dmbt1 protein, mouse; D016023:Integrins; D009077:Mucins; D025521:Tumor Suppressor Proteins