ATP Driven Pumps III: V-type Pumps

V-type pumps are ATP-driven pumps found in the vacuolar membranes of plants, yeast, endosomal and lysosomal membranes of animal cells, plasma membranes of a few specialized eukaryotic cells, and some prokaryotes. They are also known as the V₁V_o-ATPase, that couple ATP hydrolysis to transport protons against a concentration gradient.

The peripheral or cytosolic V₁ domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V₀ domain containing at least five subunits helps transport protons. This proton translocation activity is vital for cellular processes such as pH homeostasis, endocytosis, protein trafficking, urine acidification, and neurotransmitter release.

While complete loss of the pump function can be lethal, mutations in the subunits are associated with renal tubular acidosis, osteoporosis, neurodegenerative disease, and others, making this pump a potential drug target.

Regulation of the pumps’ activity by different mechanisms ensures that the cell and its organelles maintain the proton gradient. The reversible dissociation of the V₀ and V₁ domains is due to several factors like nutrients and growth factors that can silence the activity of both subunits. For instance, the reversible disulfide bond formation at the cysteine residues of the A-subunit does not allow ATP hydrolysis to occur.

Modulation of the pump density is another control mechanism seen in epithelial cells. In renal epithelial cells, proton transport in alpha intercalated and epididymal clear cells is controlled by reversible fusion of intracellular vesicles containing a high density of V-type pumps with the apical membrane.