Tripodi G, Valtorta F, Torielli L, Chieregatti E, Salardi S, Trusolino L, Menegon A, Ferrari P, Marchisio P C, Bianchi G
Prassis-Sigma Tau Research Institute, Settimo M.se, Milan, Italy.
J Clin Invest. 1996 Jun 15;97(12):2815-22. doi: 10.1172/JCI118737.
The adducin heterodimer is a protein affecting the assembly of the actin-based cytoskeleton. Point mutations in rat adducin alpha (F316Y) and beta (Q529R) subunits are involved in a form of rat primary hypertension (MHS) associated with faster kidney tubular ion transport. A role for adducin in human primary hypertension has also been suggested. By studying the interaction of actin with purified normal and mutated adducin in a cell-free system and the actin assembly in rat kidney epithelial cells (NRK-52E) transfected with mutated rat adducin cDNA, we show that the adducin isoforms differentially modulate: (a) actin assembly both in a cell-free system and within transfected cells; (b) topography of alpha V integrin together with focal contact proteins; and (c) Na-K pump activity at V(max) (faster with the mutated isoforms, 1281 +/- 90 vs 841 +/- 30 nmol K/h.mg pt., P < 0.0001). This co-modulation suggests a role for adducin in the constitutive capacity of the epithelia both to transport ions and to expose adhesion molecules. These findings may also lead to the understanding of the relation between adducin polymorphism and blood pressure and to the development of new approaches to the study of hypertension-associated organ damage.
内收蛋白异二聚体是一种影响基于肌动蛋白的细胞骨架组装的蛋白质。大鼠内收蛋白α亚基（F316Y）和β亚基（Q529R）中的点突变与一种大鼠原发性高血压（MHS）有关，这种高血压与肾小管离子转运加快有关。也有人提出内收蛋白在人类原发性高血压中起作用。通过在无细胞系统中研究肌动蛋白与纯化的正常和突变型内收蛋白的相互作用，以及在用突变型大鼠内收蛋白cDNA转染的大鼠肾上皮细胞（NRK-52E）中的肌动蛋白组装，我们发现内收蛋白亚型有差异地调节：（a）无细胞系统和转染细胞内的肌动蛋白组装；（b）αV整合素与粘着斑蛋白的拓扑结构；以及（c）Vmax时的钠钾泵活性（突变型亚型更快，1281±90对841±30 nmol K/h.mg蛋白，P<0.0001）。这种共同调节表明内收蛋白在上皮细胞运输离子和暴露粘附分子的组成能力中起作用。这些发现也可能有助于理解内收蛋白多态性与血压之间的关系，并有助于开发研究高血压相关器官损伤的新方法。
