In animals, V-ATPases are believed to play roles in the plasma membrane, as
well as endomembrane. To understand these different functions, it is neces
sary to adopt a genetic approach in a physiologically tractable model organ
ism. For this purpose, Drosophila melanogaster is ideal, because of the pow
erful genetics associated with the organism and because of the unusually in
formative epithelial phenotype provided by the Malpighian tubule. Recently,
the first animal "knockouts" of a V-ATPase were described in Drosophila. T
he resulting phenotypes have general utility for our understanding of V-ATP
ase function and suggest a screen for novel subunits and associated protein
s. Genome project resources have accelerated our knowledge of the V-ATPase
gene family size and the new Drosophila genes vhaSFD, vha100-1, vha100-2, v
ha100-3, vha16-2, vha16-3, vha16-4, vhaPPA1, vhaPPA2, vhaM9.7.1, and vhaM9.
7.2 are described. The Drosophila V-ATPase model is thus well-suited to bot
h forward and reverse genetic analysis of this complex multifunctional enzy
me.