title: Genetic studies of spectrin in the larval fat body of Drosophila melanogaster: evidence for a novel lipid uptake apparatus.
abstract: Spectrin cytoskeleton defects produce a host of phenotypes affecting the plasma membrane, cell polarity, and secretory membrane traffic. However, many of the underlying molecular mechanisms remain unexplained by prevailing models. Here we used the larval fat body of Drosophila melanogaster as a genetic model system to further elucidate mechanisms of αβ-spectrin function. The results provide unexpected new insights into spectrin function as well as mechanisms of dietary fat uptake and storage. We show that loss of α- or β-spectrin in the fat body eliminated a population of small cortical lipid droplets and altered plasma membrane architecture, but did not affect viability of the organism. We present a novel model in which αβ-spectrin directly couples lipid uptake at the plasma membrane to lipid droplet growth in the cytoplasm. In contrast, strong overexpression of β-spectrin caused fat body atrophy and larval lethality. Overexpression of β-spectrin also perturbed transport of dietary fat from the midgut to the fat body. This hypermorphic phenotype appears to be the result of blocking secretion of the lipid carrier lipophorin from fat cells. However, this midgut phenotype was never seen with spectrin loss of function, suggesting that spectrin is not normally required for lipophorin secretion or function. The β-spectrin hypermorphic phenotype was ameliorated by co-overexpression of α-spectrin. Based on the overexpression results here, we propose that β-spectrin family members may be prone to hypermorphic effects (including effects on secretion) if their activity is not properly regulated.
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607.
authors.forename: Bianca
authors.initials: B
authors.lastname: Diaconeasa
authors.forename: G Harper
authors.initials: GH
authors.lastname: Mazock
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Mahowald
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Dubreuil
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001693:Biological Transport, Active / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D005216:Fat Body / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D018628:Gene Dosage; D055785:Gene Knockdown Techniques; D017344:Genes, Insect; D007814:Larva / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D013049:Spectrin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D013049:Spectrin
keywords: larval fat body; lipid transport; lipophorin; perilipin; spectrin
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