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

Phenotypic plasticity and terminal differentiation of the intercalated cell: the hensin pathway.
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嵌入细胞的表型可塑性和终末分化:hensin 途径。

DOI:
10.1159/000020650
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发表时间:
2000
期刊:
Experimental nephrology
影响因子:
--
通讯作者:
Wiederholt,T
Wiederholt,T
中科院分区:
--
文献类型:
--
作者:
Al-Awqati,Q;Vijayakumar,S;Takito,J;Hikita,C;Yan,L;Wiederholt,T

文献摘要

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收集小管的插层细胞存在于多种类型的光谱中。α型通过顶部的H+ atp酶和基底侧的Cl: hco3交换剂分泌酸,后者是红细胞带3 (kAE1)的一种选择性剪接形式,而β型通过在反膜上有这些转运体分泌hco3。在β型克隆细胞系中,我们发现播种密度会导致这种转化。在高密度细胞的细胞外基质中沉积了一种新的蛋白质,称为hensin,纯化后可以逆转转运蛋白的极性。Hensin还诱导了微绒毛蛋白、绒毛蛋白的表达,并引起了顶端末端网蛋白、细胞角蛋白19和肌动蛋白的出现,这些都导致了微绒毛结构的繁荣发展。此外,母鸡素使β细胞呈柱状。所有这些研究都表明,至少在体外,插层细胞的极性转换代表了终末分化,而母鸡素是介导这一过程的新途径中的第一个蛋白质。Hensin, DMBT1, CRP-ductin和ebnerin是位于人类染色体10q25-26上的单个基因的交替剪接产物,该区域在一些癌症,特别是恶性胶质瘤中经常被删除。Hensin在许多上皮细胞类型中表达,它可能在这些上皮细胞的分化中也起着类似的重要作用。
The intercalated cell of the collecting tubule exists in a spectrum of types. The alpha form secretes acid by an apical H+ATPase and a basolateral Cl:HCO3exchanger which is an alternatively spliced form of the red cell band 3 (kAE1), while the beta form secretes HCO3by having these transporters on the reverse membranes. In a clonal cell line of the beta form we found that seeding density causes this conversion. A new protein, termed hensin, was deposited in the extracellular matrix of high-density cells which on purification reversed the polarity of the transporters. Hensin also induced the expression of the microvillar protein, villin, and caused the appearance of 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 studies 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 cancers, 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.