A Slow pH-dependent Conformational Transition Underlies a Novel Mode of Activation of the Epithelial Na+/H+ Exchanger-3 Isoform

摘要: Abstract Allosteric control of Na+/H+ exchange by intracellular protons ensures rapid and accurate regulation the pH. Although this allosteric effect was heretofore thought to occur almost instantaneously, we report here occurrence a slower secondary activation epithelial exchanger (NHE)-3 isoform. This slow mode developed over course minutes unique NHE3 closely related isoform NHE5, but not observed in NHE1 or NHE2. Activation due increased density exchangers at cell surface, nor it accompanied detectable changes phosphorylation. The association with cytoskeleton, assessed its retention detergent-insoluble fraction, similarly unaffected acidification. In contrast progressive elicited acidification, deactivation occurred very rapidly upon restoration physiological We propose that undergoes pH-dependent transition from less active more state, likely changing conformation state association.