AS160: a new Na,K‐ATPase partner that regulates the trafficking of the sodium pump in response to energy depletion and renal ischemia

Abstract

The Na,K‐ATPase appears to be located in two different cellular pools. The major sodium pump pool is located at the plasma membrane, while the other pool resides in cytoplasmic vesicular compartments which can translocate to the plasma membrane in response to physiological stimuli. We have identified AS160 as a new Na,K‐ATPase partner. We also demonstrated that the knockdown of AS160 increases the level of cellular Na,K‐ATPase activity, suggesting that AS160 modulates the activity of the enzyme. In the present study we characterized aspects of the physiological role of the interaction between AS160 and Na,K‐ATPase. We find that AS160 is required for the intracellular accumulation of the Na, K‐ATPase that occurs in response to energy depletion in cultured epithelial cells. In intact animals ischemic kidney injury has been shown to induce internalization of the Na,K‐ATPase from the plasma membranes of renal epithelial cells. We assessed the distribution of the Na,K‐ATPase following renal ischemia and reperfusion in kidneys from wild type and AS160 knockout mice. We observed a substantial decrease in the injury‐induced cytoplasmic accumulation of the Na,K‐ATPase in the renal epithelial cells of the AS160 knockout mice as compared to those of the wild type controls. We propose that AS160 plays a key role in regulating the redistribution of the Na,K‐ATPase that occurs in response to energy depletion and renal ischemia.