Myosin VI physically and functionally interacts with NHE3 in the renal proximal tubule

The Na+/H+ exchanger isoform 3 (NHE3) is responsible for most sodium, bicarbonate, chloride, and water reabsorption in the renal proximal tubule (PT), thereby playing an essential role in acid-base, extracellular volume homeostasis, and blood pressure regulation. NHE3 activity is modulated by several mechanisms, including the redistribution of the transporter between the body of the microvilli (where NHE3 is active) and the base of the microvilli (where NHE3 is phosphorylated at serine 552 and is less active). Despite the well-characterized physiological and pharmacological importance of the subcellular distribution of NHE3, the exact mechanism whereby NHE3 is translocated along microvilli microdomains of the proximal tubule apical membrane is unknown.