[Regulation of the luminal Na+/H+ exchanger NHE3 by intracellular protein trafficking].
The article summarizes some of the recent developments in the understanding of the mechanisms of regulation of the proximal tubule apical membrane Na+/H+ antiporter NHE3. NHE3 antiporter has a major role in HCO3- and NaCl reabsorption in the proximal tubule. NHE3 protein is associated with the regulatory factor NHERF which interacts with ezrin, an actin-binding protein. This multi-protein complex constitutes a link between a membrane protein, NHE3, and actin cytoskeleton. Cytoskeleton organization has a key role to control NHE3 activity under normal conditions. Pharmacological perturbations of actin polymerization interfere with NHE3 activity. Parathyroid hormone-induced NHE3 activity inhibition results first, from a protein kinase A-mediated phosphorylation without protein trafficking, and then from endocytosis involving dynamin. The stimulatory effect of systemic angiotensin II concentrations on NHE3 activity is protein kinase C-dependent and results, at least in part, from exocytic insertion of the protein in luminal membranes. It requires cytoskeleton integrity.
du Cheyron
D
D
INSERM U356, IFR58, Université Paris VI, Paris.
Paillard
M
M
Poggioli
J
J
D000818:Animals; D003599:Cytoskeleton / Q000502:physiology; D006801:Humans; D007684:Kidney Tubules / Q000502:physiology*; D008954:Models, Biological; D021381:Protein Transport / Q000502:physiology*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
C000613385:SLC9A3 protein, human; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers