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) 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.
Suh
Jae Myoung
JM
Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
Stenesen
Drew
D
Peters
John M
JM
Inoue
Akiko
A
Cade
Angela
A
Graff
Jonathan M
JM
D020121:5' Untranslated Regions; D000818:Animals; D030801:Animals, Genetically Modified; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D005216:Fat Body / Q000502:physiology; D007814:Larva / Q000502:physiology; D008136:Longevity; D009154:Mutation; D009842:Oligopeptides / Q000737:chemistry*; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000502:physiology*
D020121:5' Untranslated Regions; D002352:Carrier Proteins; D009842:Oligopeptides; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; C097755:arginyl-glycyl-serine