Vijayakumar S, Takito J, Hikita C, Al-Awqati Q
Department of Medicine and Department of Physiology, College of Physicians and Surgeons of Columbia University, New York 10032, USA.
J Cell Biol. 1999 Mar 8;144(5):1057-67. doi: 10.1083/jcb.144.5.1057.
Intercalated epithelial cells exist in a spectrum of phenotypes; at one extreme, beta cells secrete HCO3 by an apical Cl/HCO3 exchanger and a basolateral H+ ATPase. When an immortalized beta 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.
闰管上皮细胞存在一系列表型；在一个极端情况下，β细胞通过顶端的Cl⁻/HCO₃⁻交换体和基底外侧的H⁺ATP酶分泌HCO₃⁻。当一个永生化β细胞系以高密度接种时，它会在其细胞外基质（ECM）中沉积一种新蛋白质——hensin，该蛋白质可使包括Cl⁻/HCO₃⁻交换体（带3的一种可变剪接形式）和质子转运ATP酶在内的几种蛋白质的极性发生反转。当以低密度接种并使其形成单层时，这些极化上皮细胞维持这两种蛋白质的原始分布。尽管这些细胞合成并分泌hensin，但它并不保留在ECM中，而是存在于大量细胞内囊泡中。低密度细胞的顶端细胞质缺乏肌动蛋白、绒毛蛋白和细胞角蛋白19。扫描电子显微镜显示这些细胞有稀疏的微绒毛，而高密度细胞有丰富的顶端表面内褶和微绒毛。高密度细胞的顶端细胞质含有高水平的肌动蛋白、细胞角蛋白19和绒毛蛋白。这两种表型的细胞形状不同，高密度细胞高且横截面积小，而低密度细胞低且扁平。这种柱状化和顶端细胞质的重塑依赖于hensin；它可通过将低密度细胞接种在由高密度细胞预处理过的滤膜上诱导产生，并可被hensin抗体阻止。细胞形状和顶端细胞骨架的变化让人联想到在肠道和其他上皮细胞终末分化过程中发生的过程。Hensin在肠道和前列腺（两个存在持续分化过程的器官）中高度表达。Hensin在肠道分化程度较低的隐窝细胞和前列腺基底细胞中的表达与低密度细胞相似；即细胞内囊泡丰富但不在ECM中定位。另一方面，与高密度细胞一样，hensin仅位于终末分化的吸收性绒毛细胞和前列腺腔细胞的ECM中。这些研究表明，hensin是闰管细胞以及可能其他上皮细胞终末分化中的一个关键新分子。
