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Shear stress-induced changes of membrane transporter localization and expression in mouse proximal tubule cells
Yi Duan, Alan M. Weinstein, Sheldon Weinbaum and Tong Wang
Proceedings of the National Academy of Sciences of the United States of America
Vol. 107, No. 50 (December 14, 2010), pp. 21860-21865
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/25756974
Page Count: 6
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Our previous studies of microperfused single proximal tubule showed that flow-dependent Na⁺ and HCO₃⁻ reabsorption is due to a modulation of both NHE3 and vacuolar H⁺-ATPase (V-ATPase) activity. An intact actin cytoskeleton was indicated to provide a structural framework for proximal tubule cells to transmit mechanical forces and subsequently modulate cellular functions. In this study, we have used mouse proximal tubule (MPT) cells as a model to study the role of fluid shear stress (FSS) on apical NHE3 and V-ATPase and basolateral Na/K-ATPase trafficking and expression. Our hypothesis is that FSS stimulates both apical and basolateral transporter expression and trafficking, which subsequently mediates salt and volume reabsorption. We exposed MPT cells to 0.2 dynes/cm² FSS for 3 h and performed confocal microscopy and Western blot analysis to compare the localization and expression of both apical and basolateral transporters in control cells and cells subjected to FSS. Our findings show that FSS leads to an increment in the amount of protein expression, and a translocation of apical NHE3 and V-ATPase from the intracellular compartment to the apical plasma membrane and Na/K-ATPase to the basolateral membrane. Disrupting actin by cytochalasin D blocks the FSS-induced changes in NHE3 and Na/K-ATPase, but not V-ATPase. In contrast, FSS-induced V-ATPase redistribution and expression are largely inhibited by colchicine, an agent that blocks microtubule polymerization. Our findings suggest that the actin cytoskeleton plays an important role in FSS-induced NHE3 and Na/K-ATPase trafficking, and an intact microtubule network is critical in FSS-induced modulation of V-ATPase in proximal tubule cells.
Proceedings of the National Academy of Sciences of the United States of America © 2010 National Academy of Sciences