Phenotypic plasticity and terminal differentiation of the intercalated cell: The hensin pathway

The intercalated cell of the collecting tubule exists in a spectrum of type s. The alpha form secretes acid by an apical H+ ATPase and a basolateral CI :HCO3 exchanger which is an alternatively spliced form of the red cell band 3 (kAE1), while the beta form secretes HCO3 by having these transporters o n the reverse membranes. In a clonal cell line of the beta form we found th at seeding density causes this conversion. A new protein, termed hensin, wa s deposited in the extracellular matrix of high-density cells which on puri fication reversed the polarity of the transporters. Hensin also induced the expression of the microvillar protein, villin, and caused the appearance o f the apical terminal web proteins, cytokeratin 19 and actin, all of which led to the development of an exuberant microvillar structure. In addition, hensin caused the beta cells to assume a columnar shape. All of these studi es demonstrate that the conversion of polarity in the intercalated cell, at least in vitro, represents terminal differentiation and that hensin is the first protein in a new pathway that mediates this process. Hensin, DMBT1, CRP-ductin, and ebnerin are alternately spliced products from a single gene located on human chromosome 10q25-26, a region often deleted in several ca ncers, especially malignant gliomas. Hensin is expressed in many epithelial cell types, and it is possible that it plays a similarly important role in the differentiation of these epithelia as well. Copyright (C) 2000 S. Karg er AG,Basel.