Structural determinants and significance of regulation of electrogenic Na(+)-HCO(3)(-) cotransporter stoichiometry.
Na(+)-HCO(3)(-) cotransporters play an important role in intracellular pH regulation and transepithelial HCO(3)(-) transport in various tissues. Of the characterized members of the HCO(3)(-) transporter superfamily, NBC1 and NBC4 proteins are known to be electrogenic. An important functional property of electrogenic Na(+)-HCO(3)(-) cotransporters is their HCO(3)(-):Na(+) coupling ratio, which sets the transporter reversal potential and determines the direction of Na(+)-HCO(3)(-) flux. Recent studies have shown that the HCO(3)(-):Na(+) transport stoichiometry of NBC1 proteins is either 2:1 or 3:1 depending on the cell type in which the transporters are expressed, indicating that the HCO(3)(-):Na(+) coupling ratio can be regulated. Mutational analysis has been very helpful in revealing the molecular mechanisms and signaling pathways that modulate the coupling ratio. These studies have demonstrated that PKA-dependent phosphorylation of the COOH terminus of NBC1 proteins alters the transport stoichiometry. This cAMP-dependent signaling pathway provides HCO(3)(-) -transporting epithelia with an efficient mechanism for modulating the direction of Na(+)-HCO(3)(-) flux through the cotransporter.
Gross
Eitan
E
Departments of Urology and Physiology and Biophysics, Case Western Reserve University, and Veterans Affairs Medical Center, Cleveland, Ohio 44106, USA.
Kurtz
Ira
I
D000818:Animals; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008954:Models, Biological; D027982:Sodium-Bicarbonate Symporters / Q000737:chemistry* / Q000378:metabolism*
D027982:Sodium-Bicarbonate Symporters