Role of integrins in the assembly and function of hensin in intercalated cells

J Am Soc Nephrol. 2008 Jun;19(6):1079-91. doi: 10.1681/ASN.2007070737. Epub 2008 Mar 12.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calcium-Binding Proteins
  • Cell Differentiation
  • DNA-Binding Proteins
  • Epithelial Cells / cytology*
  • Integrins / physiology*
  • Kidney / cytology*
  • Mice
  • Mucins / physiology*
  • Tumor Suppressor Proteins

Substances

  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Dmbt1 protein, mouse
  • Integrins
  • Mucins
  • Tumor Suppressor Proteins