RT Journal Article
SR Electronic
T1 Akt Substrate of 160 kD Regulates Na<sup>+</sup>,K<sup>+</sup>-ATPase Trafficking in Response to Energy Depletion and Renal Ischemia
JF Journal of the American Society of Nephrology
JO J. Am. Soc. Nephrol.
FD American Society of Nephrology
SP 2765
OP 2776
DO 10.1681/ASN.2013101040
VO 26
IS 11
A1 Alves, Daiane S.
A1 Thulin, Gunilla
A1 Loffing, Johannes
A1 Kashgarian, Michael
A1 Caplan, Michael J.
YR 2015
UL http://jasn.asnjournals.org/content/26/11/2765.abstract
AB Renal ischemia and reperfusion injury causes loss of renal epithelial cell polarity and perturbations in tubular solute and fluid transport. Na+,K+-ATPase, which is normally found at the basolateral plasma membrane of renal epithelial cells, is internalized and accumulates in intracellular compartments after renal ischemic injury. We previously reported that the subcellular distribution of Na+,K+-ATPase is modulated by direct binding to Akt substrate of 160 kD (AS160), a Rab GTPase-activating protein that regulates the trafficking of glucose transporter 4 in response to insulin and muscle contraction. Here, we investigated the effect of AS160 on Na+,K+-ATPase trafficking in response to energy depletion. We found that AS160 is required for the intracellular accumulation of Na+,K+-ATPase that occurs in response to energy depletion in cultured epithelial cells. Energy depletion led to dephosphorylation of AS160 at S588, which was required for the energy depletion–induced accumulation of Na,K-ATPase in intracellular compartments. In AS160-knockout mice, the effects of renal ischemia on the distribution of Na+,K+-ATPase were substantially reduced in the epithelial cells of distal segments of the renal tubules. These data demonstrate that AS160 has a direct role in linking the trafficking of Na+,K+-ATPase to the energy state of renal epithelial cells.