Regulation of longevity by regulator of G-protein signaling protein, Loco.
Regulator of G-protein signaling (RGS) proteins contribute to G-protein signaling pathways as activators or repressors with GTPase-activating protein (GAP) activity. To characterize whether regulation of RGS proteins influences longevity in several species, we measured stress responses and lifespan of RGS-overexpressing and RGS-lacking mutants. Reduced expression of Loco, a RGS protein of Drosophila melanogaster, resulted in a longer lifespan for both male and female flies, also exhibiting stronger resistance to three different stressors (starvation, oxidation, and heat) and higher manganese-containing superoxide dismutase (MnSOD) activity. In addition, this reduction in Loco expression increased fat content and diminished cAMP levels. In contrast, overexpression of both genomic and cDNA loco gene significantly shortened the lifespan with weaker stress resistance and lower fat content. Deletion analysis of the Loco demonstrated that its RGS domain is required for the regulation of longevity. Consistently, when expression of RGS14, mammalian homologue of Loco, was reduced in rat fibroblast cells, the resistance to oxidative stress increased with higher MnSOD expression. The changes of yeast Rgs2 expression, which shares a conserved RGS domain with the fly Loco protein, also altered lifespan and stress resistance in Saccharomyces cerevisiae. Here, we provide the first evidence that RGS proteins with GAP activity affect both stress resistance and longevity in several species.
Department of Cell Biology and Molecular Medicine, UMDNJ-New Jersey Medical School, Newark, 07101, USA.
Yuh-Ru
YR
Lin
Keetae
K
Kim
Yanfei
Y
Yang
Andreas
A
Ivessa
Junichi
J
Sadoshima
Yongkyu
Y
Park
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D017124:Conserved Sequence; D000242:Cyclic AMP / Q000096:biosynthesis; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020549:GTP Phosphohydrolase Activators / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression; D008136:Longevity / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D015398:Signal Transduction; D013312:Stress, Physiological; D013482:Superoxide Dismutase / Q000096:biosynthesis
D029721:Drosophila Proteins; D020549:GTP Phosphohydrolase Activators; C119015:LOCO protein, Drosophila; D009419:Nerve Tissue Proteins; D020710:RGS Proteins; C106374:Rgs14 protein, rat; D000242:Cyclic AMP; D013482:Superoxide Dismutase