The Rab-GAP TBC1D4 (AS160) is dispensable for the control of sodium and water homeostasis but regulates GLUT4 in mouse kidney.

The Rab-GAP TBC1D4 (AS160) is dispensable for the control of sodium and water homeostasis but regulates GLUT4 in mouse kidney. Am J Physiol Renal Physiol. 2015 Sep 2;:ajprenal.00139.2015 Authors: Di Chiara M, Glaudemans B, Loffing-Cueni D, Odermatt A, Al-Hasani H, Devuyst O, Faresse N, Loffing J Abstract The Rab GTPase-activating protein TBC1D4 (AS160) controls trafficking of the glucose transporter GLUT4 in adipocytes and skeletal muscle cells. TBC1D4 is also highly abundant in the renal distal tubule, although its role in this tubule is so far unknown. In vitro studies suggest that it is involved in the regulation of renal transporters and channels such as ENaC, AQP2 and the Na(+)-K(+)-ATPase. To assess the physiological role of TBC1D4 in the kidney, wild-type (TBC1D4(+/+)) and TBC1D4-deficient (TBC1D4(-/-)) mice were studied. Unexpectedly, neither under standard nor under challenging conditions (low Na(+)/high K(+), water restriction) did TBC1D4-deficient mice show any difference in urinary Na(+) and K(+) excretion, urine osmolarity, plasma ion and aldosterone levels, and blood pressure when compared to TBC1D4(+/+) mice. Also immunoblotting did not reveal any change in the abundance of major renal sodium and water transporting proteins (NKCC2, NCC, ENaC, AQP2, and the Na(+)-K(+)-ATPase). However, the abundance of GLUT4, which co-localizes with TBC1D4 along the distal nephron of TBC1D4(+/+) mice, was lower in whole kidney lysates o...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research