Dissociation and redistribution of Na+,K+-ATPase from its surface membrane actin cytoskeletal complex during cellular ATP depletion

B. A. Molitoris, A. Geerdes, J. R. McIntosh

Research output: Contribution to journalArticle

123 Scopus citations


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 metabolic-ally 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+-ATP-ase to the apical membrane. During ATP depletion, total cellular Na+,K+-ATPase activity was unaltered, but the TritonX-100-insoluble fraction (cytoskeleton associated) of Na+,K+-ATPase activity decreased (P < 0.01), with a corresponding increase in the detergent-soluble fraction of Na+,K+-ATPase (P < 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.

Original languageEnglish (US)
Pages (from-to)462-469
Number of pages8
JournalJournal of Clinical Investigation
Issue number2
StatePublished - Aug 1991
Externally publishedYes


  • Acute renal failure
  • Ankyrin ischemia
  • Cytoskeleton
  • Epithelial polarity

ASJC Scopus subject areas

  • Medicine(all)

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