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

Abstract

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 < 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. (J. Clin. Invest. 1991.

Cell death induced by acute renal injury: a perspective on the contributions of apoptosis and necrosis

“…Disruption of the cortical actin cytoskeleton leads to redistribution of Na ϩ -K ϩ -ATPase to the apical membrane of the proximal tubule epithelial cell, and this will alter the Na ϩ handling of the proximal tubule (155,157). A high fraction of filtered Na ϩ will reach the macula densa and result in increased vasoconstriction via the tubuloglomerular feedback mechanism (153).…”

The interaction of N-formyl peptide chemoattractant receptors with the membrane skeleton is energy-dependent

“…The interaction of other membrane proteins with the membrane skeleton, e.g. Na+, K•-ATPase, has also been shown to be energy-dependent [11]. Therefore, we studied the effect of energy depletion on immobilization of FPR to the membrane skeleton.…”

Akt Substrate of 160 kD Regulates Na+,K+-ATPase Trafficking in Response to Energy Depletion and Renal Ischemia

“…23 Na, K-ATPase is internalized and retained in intracellular compartments in response to energy depletion and renal ischemia. 7,15 To investigate whether AS160 plays a role in this Na,K-ATPase redistribution after energy depletion, we examined the effects of energy depletion on the subcellular distribution of the Na,K-ATPase in a stable clonal cell line in which AS160 is robustly knocked down by small hairpin RNA (shRNA) (AS160 KD). 23 Wild-type (WT) Madin-Darby Canine Kidney (MDCK) cells or AS160 KD MDCK cells were subjected or not to energy depletion.…”

“…[2][3][4] Physiologic stimuli can promote Na,K-ATPase endocytosis or translocation from the intracellular pool to the plasma membrane. 2,[5][6][7] The glucose transporter 4 (GLUT4) of muscle and fat cells is one of the best-studied examples of a transport protein whose activity is governed through stimulus-induced trafficking between the plasma membrane and intracellular compartments. 8 GLUT4 is delivered to the cell surface from intracellular storage vesicles in response to stimuli that favor increased glucose uptake, including insulin and muscle contraction.…”

“…[16][17][18] AKI is associated with detachment of the sodium pump from the plasma membrane's subcortical cytoskeleton and with the loss of cell polarity and resultant impairment of renal function. 7,[19][20][21] Recovery from ischemic renal injury involves restitution of cellular polarity and return of the sodium pump from intracellular compartments to the plasma membrane. 22 Recently, we reported that AS160 interacts directly with the Na,K-ATPase a-subunit and modulates the sodium pump's subcellular distribution.…”