Loss of G2subunit of vacuolar-type proton transporting ATPase leads to G1subunit upregulation in the brain

Abstract

Vacuolar-type ATPase (V-ATPase) is a primary proton pump with versatile functions in various tissues. In nerve cells, V-ATPase is required for accumulation of neurotransmitters into secretory vesicles and subsequent release at the synapse. Neurons express a specific isoform (G2) of the G subunit of V-ATPase constituting the catalytic sector of the enzyme complex. Using gene targeting, we generated a mouse lacking functional G2(G2 null), which showed no apparent disorders in architecture and behavior. In the G2-null mouse brain, a G1subunit isoform, which is ubiquitously expressed in neuronal and non-neuronal tissues, accumulated more abundantly than in wild-type animals. This G1upregulation was not accompanied by an increase in mRNA. These results indicate that loss of function of neuron-specific G2isoform was compensated by an increase in levels of the G1isoform without apparent upregulation of the G1mRNA.