Revisiting the Role of Ser982 Phosphorylation in Stoichiometry Shift of the Electrogenic Na/HCO Cotransporter NBCe1.

In most cell types and heterologous expression systems, the electrogenic sodium-bicarbonate cotransporter NBCe1 operates with a 1Na-2HCO stoichiometry that, given typical transmembrane electrochemical gradients, promotes Na+ and HCO influx. However, NBCe1 in the kidney mediates HCO efflux (HCO reabsorption), a direction that has been predicted to be favored only if NBCe1 operates with a 1:3 stoichiometry. The phosphorylation state of Ser982 in the cytosolic carboxy-terminal domain of NBCe1 has been reported to be a key determinant of the transporter stoichiometry, with non-phosphorylated Ser982 favoring a 1:3 stoichiometry.

Extrarenal Signs of Proximal Renal Tubular Acidosis Persist in Nonacidemic Nbce1b/c-Null Mice.

Background: The gene encodes electrogenic sodium bicarbonate cotransporter 1 (NBCe1). Inheritance of recessive mutations in causes proximal renal tubular acidosis (pRTA), a disease characterized by metabolic acidosis, growth retardation, ocular abnormalities, and often dental abnormalities. Mouse models of pRTA exhibit acidemia, corneal edema, weak dental enamel, impacted colons, nutritional defects, and a general failure to thrive, rarely surviving beyond weaning.