An RGS-containing sorting nexin controls Drosophila lifespan

The pursuit of eternal youth has existed for centuries and recent data indicate that fat-storing tissues control lifespan. In a D. melanogaster fat body insertional mutagenic enhancer trap screen designed to isolate genes that control longevity, we identified a regulator of G protein signaling (RGS)...

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Bibliographic Details
Published in:PloS one 2008-05, Vol.3 (5), p.e2152-e2152
Main Authors: Suh, Jae Myoung, Stenesen, Drew, Peters, John M, Inoue, Akiko, Cade, Angela, Graff, Jonathan M
Format: Article
Language:English
Subjects:
5' Untranslated Regions
Adipocytes
Aging
Animals
Animals, Genetically Modified
Bacteria
Carrier Proteins - chemistry
Carrier Proteins - physiology
Developmental biology
Developmental Biology/Aging
Developmental Biology/Cell Differentiation
Diabetes and Endocrinology/Obesity
Diabetes and Endocrinology/Type 2 Diabetes
Drosophila
Drosophila - genetics
Drosophila - physiology
Drosophila melanogaster
Fat body
Fat Body - physiology
G proteins
Genes
Genetic engineering
Genetics and Genomics/Gene Discovery
Insects
Insulin resistance
Larva - physiology
Life span
Longevity
Mammals
Metabolic disorders
Mutants
Mutation
Nexin
Oligopeptides - chemistry
Physiology/Membranes and Sorting
Proteins
Sorting Nexins
Stem cells
Tissues
Transcription factors
Vesicular Transport Proteins - chemistry
Vesicular Transport Proteins - physiology
Youth
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Summary:The pursuit of eternal youth has existed for centuries and recent data indicate that fat-storing tissues control lifespan. In a D. melanogaster fat body insertional mutagenic enhancer trap screen designed to isolate genes that control longevity, we identified a regulator of G protein signaling (RGS) domain containing sorting nexin, termed snazarus (sorting nexin lazarus, snz). Flies with insertions into the 5' UTR of snz live up to twice as long as controls. Transgenic expression of UAS-Snz from the snz Gal4 enhancer trap insertion, active in fat metabolic tissues, rescued lifespan extension. Further, the lifespan extension of snz mutants was independent of endosymbiont, e.g., Wolbachia, effects. Notably, old snz mutant flies remain active and fertile indicating that snz mutants have prolonged youthfulness, a goal of aging research. Since mammals have snz-related genes, it is possible that the functions of the snz family may be conserved to humans.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0002152