Received July 6, 2007
Accepted on November 25, 2007

BASIC RESEARCH

Role of Integrins in the Assembly and Function of Hensin in Intercalated Cells

Soundarapandian Vijayakumar ^*1, Hediye Erdjument-Bromage , Paul Tempst , and Qais Al-Awqati ^*

*Departments of Medicine and Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, and Laboratory of Protein Chemistry, Memorial Sloan-Kettering Cancer Center, New York, New York

¹ To whom correspondence should be addressed. E-mail: soundarapandian_vijayakumar{at}urmc.rochester.edu.

	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 1 were used to demonstrate that activation of integrin v1 causes deposition of hensin in the ECM. Once hensin polymerizes and deposits into the ECM, it binds to integrin 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: v1 generates polymerized hensin, and another set of integrins (containing 6) mediates signals between hensin and the interior of the cells.