MOLECULAR-GENETIC ANALYSIS OF V-ATPASE FUNCTION IN DROSOPHILA-MELANOGASTER

V-ATPases are phylogenetically widespread, highly conserved, multisubu nit proton pumps. Originally characterised in endomembranes, they have been found to energise transport across plasma membranes in a range o f animal cells and particularly in certain epithelia. While yeast is t he model of choice for the rapid generation and identification of V-AT Pase mutants, it does not allow their analysis in a plasma membrane co ntext. For such purposes, Drosophila melanogaster is a uniquely suitab le model, Accordingly, we have cloned and characterised genes encoding several V-ATPase subunits in D. melanogaster and, using P-element tec hnology, we have succeeded in generating multiple new alleles, Reporte r gene constructs reveal ubiquitous expression, but at particularly hi gh levels in those epithelia thought to be energised by V-ATPases, and several of the alleles have lethal recessive phenotypes characterised by epithelial dysfunction, These results, while providing the first g ene knockouts of V-ATPases in animals, also illustrate the general uti lity of D. melanogaster as a model for the genetic analysis of ion tra nsport and its control in epithelia.