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J. Cell Biol.,
Volume 144, Number 5, March 8, 1999 1057-1067
Department of Medicine and Department of Physiology, College of Physicians and Surgeons of Columbia University, New York
10032
Intercalated epithelial cells exist in a spectrum of phenotypes; at one extreme, 
cells secrete
HCO3 by an apical Cl/HCO3 exchanger and a basolateral H+ ATPase. When an immortalized cell line is
seeded at high density it deposits in its extracellular
matrix (ECM) a new protein, hensin, which can reverse
the polarity of several proteins including the Cl/HCO3
exchanger (an alternately spliced form of band 3) and the proton translocating ATPase. When seeded at low
density and allowed to form monolayers these polarized epithelial cells maintain the original distribution of
these two proteins. Although these cells synthesize and
secrete hensin, it is not retained in the ECM, but rather,
hensin is present in a large number of intracellular vesicles. The apical cytoplasm of low density cells is devoid of actin, villin, and cytokeratin19. Scanning electron microscopy shows that these cells have sparse microvilli,
whereas high density cells have exuberant apical surface infolding and microvilli. The apical cytoplasm of
high density cells contains high levels of actin, cytokeratin19, and villin. The cell shape of these two phenotypes is different with high density cells being tall with a
small cross-sectional area, whereas low density cells are
low and flat. This columnarization and the remodeling
of the apical cytoplasm is hensin-dependent; it can be
induced by seeding low density cells on filters conditioned by high density cells and prevented by an antibody to hensin. The changes in cell shape and apical cytoskeleton are reminiscent of the processes that occur
in terminal differentiation of the intestine and other epithelia. Hensin is highly expressed in the intestine and
prostate (two organs where there is a continuous process of differentiation). The expression of hensin in the
less differentiated crypt cells of the intestine and the
basal cells of the prostate is similar to that of low density cells; i.e., abundant intracellular vesicles but no localization in the ECM. On the other hand, as in high density cells hensin is located exclusively in the ECM of
the terminally differentiated absorptive villus cells and
the prostatic luminal cell. These studies suggest that
hensin is a critical new molecule in the terminal differentiation of intercalated cell and perhaps other epithelial cells.
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