Drosophila β Spectrin Functions Independently of α Spectrin to Polarize the Na,k Atpase in Epithelial Cells

Abstract

Spectrin has been proposed to function as a sorting machine that concentrates interacting proteins such as the Na,K ATPase within specialized plasma membrane domains of polarized cells. However, little direct evidence to support this model has been obtained. Here we used a genetic approach to directly test the requirement for the β subunit of the αβ spectrin molecule in morphogenesis and function of epithelial cells in Drosophila. β Spectrin mutations were lethal during late embryonic/early larval development and they produced subtle defects in midgut morphology and stomach acid secretion. The polarized distributions of αβH spectrin and ankyrin were not significantly altered in β spectrin mutants, indicating that the two isoforms of Drosophila spectrin assemble independently of one another, and that ankyrin is upstream of αβ spectrin in the spectrin assembly pathway. In contrast, β spectrin mutations had a striking effect on the basolateral accumulation of the Na,K ATPase. The results establish a role for β spectrin in determining the subcellular distribution of the Na,K ATPase and, unexpectedly, this role is independent of α spectrin.

TGF-β, Neuronal Stem Cells and Glioblastoma

“…Its striking localization to the axon hillock and axonal projection is consistent with its known involvement in axonal guidance as well as cell polarization (Dubreuil et al, 2000;Hammarlund et al, 2000;Moorthy et al, 2000).…”

ELF a β-spectrin is a neuronal precursor cell marker in developing mammalian brain; structure and organization of the elf/β-G spectrin gene

“…Its striking localization to the axon hillock and axonal projection is consistent with its known involvement in axonal guidance as well as cell polarization (Moorthy et al, 2000;Hammarlund et al, 2000;Dubreuil et al, 2000). ELF also appears to be a marker of purkinje cell precursors in the cerebellum.…”

“…For instance b-spectrin is essential in Drosophila: mutations resulting in lethality early in development (Dubreuil et al, 2000). In these mutants, basolateral distribution of the Na,K ATPase in Drosophila larval copper cells was found to be dependent upon b-spectrin function, not aspectrin, giving rise to new information on spectrin function and binding partners.…”

A mutant plasma membrane ATPase, Pma1-10, is defective in stability at the yeast cell surface

“…Indeed, stabilization of the Na ϩ ,K ϩ -ATPase of epithelial cells appears to depend on association with spectrin at the plasma membrane (30,31).…”