Dissociation and redistribution of Na+,K(+)-ATPase from its surface membrane actin cytoskeletal complex during cellular ATP depletion.
Dissociation and redistribution of Na+,K(+)-ATPase from its surface membrane actin cytoskeletal complex during cellular ATP depletion.
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DOI：
10.1172/jci115326
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发表时间：
1991-08
期刊：
影响因子：
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通讯作者：
B. A. Molitoris;A. Geerdes;J R McIntosh
中科院分区：
文献类型：
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作者：
B. A. Molitoris;A. Geerdes;J R McIntosh
Na+，K（+）-ATP酶极性分布的建立和维持对于近曲小管细胞有效的Na+重吸收是必需的，并且依赖于Na+，K（+）-ATP酶与肌动蛋白膜细胞骨架形成代谢稳定的、不溶于洗涤剂的复合物。目前的研究表明，细胞ATP耗竭导致Na+，K（+）-ATP酶从肌动蛋白细胞骨架上迅速解离，并重新分布到顶端膜。在ATP耗竭过程中，总细胞Na+，K（+）-ATPase活性不变，但Triton-X-100不溶性部分（细胞骨架相关部分）Na+，K（+）-ATPase活性降低（P <0.01），去污剂可溶性部分Na+，K（+）-ATPase活性相应升高（P <0.01）。ATP耗竭的细胞的间接免疫荧光研究显示，Na+，K（+）-ATP酶从基底外侧膜重新分布到顶膜和整个细胞质。ATP耗竭也导致F-肌动蛋白的重新分配，从一个主要的皮质浓度的核周位置。也有一个快速的，持续时间依赖性的转换单体G-肌动蛋白F-肌动蛋白开始在第一个5分钟的ATP耗竭。两者合计，这些数据表明，ATP耗竭引起深刻的细胞极性的变化，通过诱导肌动蛋白细胞骨架结构的重大变化。
Establishment and maintenance of a polar distribution of Na+,K(+)-ATPase is essential for efficient Na+ reabsorption by proximal tubule cells and is dependent upon the formation of a metabolically stable, detergent-insoluble complex of Na+,K(+)-ATPase with the actin membrane cytoskeleton. The present studies show that cellular ATP depletion results in a rapid duration-dependent dissociation of Na+,K(+)-ATPase from the actin cytoskeleton and redistribution of Na+,K(+)-ATPase to the apical membrane. During ATP depletion, total cellular Na+,K(+)-ATPase activity was unaltered, but the Triton-X-100-insoluble fraction (cytoskeleton associated) of Na+,K(+)-ATPase activity decreased (P less than 0.01), with a corresponding increase in the detergent-soluble fraction of Na+,K(+)-ATPase (P less than 0.01). Indirect immunofluorescent studies of cells with depleted ATP revealed a redistribution of Na+,K(+)-ATPase from the basolateral membrane into the apical membrane and throughout the cytoplasm. ATP depletion also resulted in the redistribution of F-actin from a primarily cortical concentration to a perinuclear location. There was also a rapid, duration-dependent conversion of monomeric G-actin to F-actin starting during the first 5 min of ATP depletion. Taken together, these data suggest that ATP depletion causes profound alterations in cell polarity by inducing major changes in the actin cytoskeletal architecture.