Activation of sterol regulatory element binding proteins in the absence of Scap in Drosophila melanogaster

The escort factor Scap is essential in mammalian cells for regulated activation of sterol regulatory element binding proteins (SREBPs). SREBPs are membrane-bound transcription factors. Cells lacking Scap cannot activate SREBP. They are therefore deficient in the transcription of numerous genes invol...

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Bibliographic Details
Published in:Genetics (Austin) 2010-05, Vol.185 (1), p.189-198
Main Authors: Matthews, Krista A, Ozdemir, Cafer, Rawson, Robert B
Format: Article
Language:English
Subjects:
Alleles
Amino acids
Animals
Caspases - metabolism
Chromosomes
Diet
Drosophila melanogaster - enzymology
Drosophila melanogaster - genetics
Drosophila melanogaster - metabolism
Drosophila Proteins - deficiency
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Embryo, Nonmammalian - cytology
Embryo, Nonmammalian - metabolism
Fluorescence
Gene Expression Regulation
Genes
Genetic Loci - genetics
Genotype
Green Fluorescent Proteins - metabolism
Immunoblotting
Investigations
Larva - cytology
Larva - metabolism
Membrane Proteins - deficiency
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mutation - genetics
Phenotype
Proteins
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
Sterol Regulatory Element Binding Proteins - metabolism
Survival Analysis
Tissue Extracts
Yeast
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Summary:The escort factor Scap is essential in mammalian cells for regulated activation of sterol regulatory element binding proteins (SREBPs). SREBPs are membrane-bound transcription factors. Cells lacking Scap cannot activate SREBP. They are therefore deficient in the transcription of numerous genes involved in lipid synthesis and uptake; they cannot survive in the absence of exogenous lipid. Here we report that, in contrast to mammalian cells, Drosophila completely lacking dscap are viable. Flies lacking dscap emerge at approximately 70% of the expected rate and readily survive as homozygous stocks. These animals continue to cleave dSREBP in some tissues. Transcription of dSREBP target genes in dscap mutant larvae is reduced compared to wild type. It is greater than in mutants lacking dSREBP and remains responsive to dietary lipids in dscap mutants. Flies lacking dscap do not require the caspase Drice to activate dSREBP. This contrasts with ds2p mutants. ds2p encodes a protease that releases the transcription factor domain of dSREBP from the membrane. Larvae doubly mutant for dscap and ds2p exhibit phenotypes similar to those of ds2p single mutants. Thus, dScap and dS2P, essential components of the SREBP activation machinery in mammalian cells, are dispensable in Drosophila owing to different compensatory mechanisms.
ISSN:1943-2631
0016-6731
1943-2631
DOI:10.1534/genetics.110.114975