Mutations of α Spectrin andlabialBlock Cuprophilic Cell Differentiation and Acid Secretion in the Middle Midgut ofDrosophilaLarvae

AbstractMutations inDrosophilaα spectrin cause larval lethality and defects in cell shape and adhesion (J. Leeet al.,1993,J. Cell Biol.123, 1797–1809). Here we examined the effects of two lethal α spectrin alleles (α-specrg41and α-specrg35) on development and function of the larval midgut. Homozygous null α-specrg41-mutant larvae exhibited a striking defect in middle midgut acidification. In contrast, many homozygous α-specrg35mutants were capable of acidification, indicating partial function of the truncated α-specrg35product. Acidification was also blocked by a mutation in thelabialgene, which is required for differentiation of cuprophilic cells in the midgut, suggesting that these cells secrete acid. We found that two isoforms of spectrin (αβ and αβH) are segregated within the basolateral and apical domains of cuprophilic cells, respectively. The most conspicuous defect in cuprophilic cells fromlabialand α spectrin mutants was in morphogenesis of the invaginated apical domain, although basolateral defects may also contribute to the acidification phenotype. Acid secretion in vertebrate systems is thought to involve the polarized activities of apical proton pumps and basolateral anion exchangers, both of which interact with spectrin. We propose that the α-specrg41mutation inDrosophilainterferes with the polarized activities of homologous molecules that drive acid secretion in cuprophilic cells