Phenotypic plasticity in the intercalated cell: the hensin pathway.
The collecting duct of the renal tubule contains two cell types, one of which, the intercalated cell, is responsible for acidification and alkalinization of urine. These cells exist in a multiplicity of morphological forms, with two extreme types, alpha and beta. The former acidifies the urine by an apical proton-translocating ATPase and a basolateral Cl/HCO3 exchanger, which is an alternately spliced form of band 3. This kidney form of band 3, kAE1, is present in the apical membrane of the beta-cell, which has the H+-ATPase on the basolateral membrane. We had suggested previously that metabolic acidosis leads to conversion of beta-types to alpha-types. To study the biochemical basis of this plasticity, we used an immortalized cell line of the beta-cell and showed that these cells convert to the alpha-phenotype when plated at superconfluent density. At high density these cells localize a new protein, which we term "hensin," to the extracellular matrix, and hensin acts as a molecular switch capable of changing the phenotype of these cells in vitro. Hensin induces new cytoskeletal proteins, makes the cells assume a more columnar shape and retargets kAE1 and the H+-ATPase. These recent studies suggest that the conversion of beta- to alpha-cells, at least in vitro, bears many of the hallmarks of terminal differentiation.
Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
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Q
Al-Awqati
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Vijayakumar
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Hikita
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J
Chen
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J
Takito
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007685:Kidney Tubules, Collecting / Q000166:cytology* / Q000276:immunology / Q000502:physiology*; D008565:Membrane Proteins; D010641:Phenotype; D006180:Proton-Translocating ATPases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000502:physiology*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D014556:Urine / Q000502:physiology
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D006180:Proton-Translocating ATPases