Topic Overview:
The vacuolar proton-secreting ATPase (V-ATPase) proton pump regulates proton secretion in the kidneys and male reproductive tract. It plays an important role in the recovery of filtered bicarbonate and excretion of non-volatile acid by the kidneys, thereby affecting pH homeostasis in cells and the whole organism. Deficient V-ATPase function in the intercalated cells of the kidney collecting duct leads to distal renal tubular acidosis, a disease process that results in kidney and systemic sequelae. In the male reproductive tract (which, like the kidney collecting duct, originates from the fetal Wolffian duct), the V-ATPase is important in the maintenance of fertility, as it is partially responsible for the physiologic luminal acidification required for proper sperm storage and maturation.

Pastor-Soler was part of the group that first characterized a novel mode of V-ATPase regulation by the bicarbonate-activated soluble adenylyl cyclase (sAC) in the epididymis in vivo, and she recently confirmed that this regulation also occurs in kidney intercalated cells. Pastor-Soler’s group was the first to show that AMP-activated protein kinase (AMPK), a metabolic sensor, could prevent sAC/protein kinase A (PKA)-mediated V-ATPase apical membrane accumulation in the epididymis and kidney cells. The group also identified an important PKA phosphorylation site in the V-ATPase A subunit and found that phosphorylation at that site is necessary and sufficient for increased activity and membrane accumulation of the pump in kidney cells. 

Pastor-Soler aims to define how PKA-dependent phosphorylation of the V-ATPase pump couples the sensing of acid-base status to proton pump activity, whereas AMPK-dependent phosphorylation may couple proton secretion to cellular metabolic status. This research could lead to new treatments for renal tubular acidosis and male infertility and to the identification of potential male contraceptive targets.