MUTATIONS OF ALPHA-SPECTRIN AND LABIAL BLOCK CUPROPHILIC CELL-DIFFERENTIATION AND ACID-SECRETION IN THE MIDDLE MIDGUT OF DROSOPHILA LARVAE

Mutations in Drosophila alpha spectrin cause larval lethality and defe cts in cell shape and adhesion (J. Lee et al., 1993, J. Cell Biol. 123 , 1797-1809). Here we examined the effects of two lethal alpha spectri n alleles (alpha-spec(rg41) and alpha.spec(rg35)) on development and f unction of the larval midgut. Homozygous null alpha-spec(rg41)-mutant larvae exhibited a striking defect in middle midgut acidification. In contrast, many homozygous alpha.spec(rg35) mutants were capable of aci dification, indicating partial function of the truncated alpha-spec(rg 35) product. Acidification was also blocked by a mutation in the labia l gene, which is required for differentiation of cuprophilic cells in the midgut, suggesting that these cells secrete acid. We found that tw o isoforms of spectrin (alpha beta and alpha beta(H)) are segregated w ithin the basolateral and apical domains of cuprophilic cells, respect ively. The most conspicuous defect in cuprophilic cells from labial an d alpha spectrin mutants was in morphogenesis of the invaginated apica l domain, although basolateral defects may also contribute to the acid ification phenotype. Acid secretion in vertebrate systems is thought t o involve the polarized activities of apical proton pumps and basolate ral anion exchangers, both of which interact with spectrin. We propose that the alpha-spe(rg41) mutation in Drosophila interferes with the p olarized activities of homologous molecules that drive acid secretion in cuprophilic cells. (C) 1998 Academic Press.