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Phenotypic plasticity in the intercalated cell: the hensin pathway.

机译:插层细胞的表型可塑性:hensin途径。

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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.
机译:肾小管的收集管包含两种细胞类型,其中一种是插层细胞,负责尿液的酸化和碱化。这些细胞以多种形态形式存在,有两种极端类型,α和β。前者通过易位质子转运ATPase和基底外侧Cl / HCO3交换剂酸化尿液,后者是条带3的交替剪接形式。条带3的肾脏形式kAE1存在于β细胞的顶膜中。 ,在基底外侧膜上具有H + -ATPase。先前我们曾提出过代谢性酸中毒会导致β型转化为α型。为了研究这种可塑性的生化基础,我们使用了永生化的β细胞细胞系,并显示了以超融合密度铺板时,这些细胞会转变为α表型。在高密度下,这些细胞将一种新蛋白(我们称为“ hensin”)定位到细胞外基质,hensin充当了能够在体外改变这些细胞表型的分子开关。 Hensin诱导新的细胞骨架蛋白,使细胞呈现更圆柱状,并重新靶向kAE1和H + -ATPase。这些最新研究表明,至少在体外,β细胞向α细胞的转化具有许多终末分化的标志。

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