Systemic and cell intrinsic roles of Gqalpha signaling in the regulation of innate immunity, oxidative stress, and longevity in Caenorhabditis elegans.
Signal transduction pathways that regulate longevity, immunity, and stress resistance can profoundly affect organismal survival. We show that a signaling module formed by the G protein alpha subunit, Gqalpha, and one of its downstream signal transducer phospholipase C beta (PLCbeta) can differentially affect these processes. Loss of Gqalpha and PLCbeta functions result in increased sensitivity to pathogens and oxidative stress but confer life span extension. Gqalpha and PLCbeta modulate life span and immunity noncell autonomously by affecting the activity of insulin/IGF1 signaling (IIS). In addition, Gqalpha and PLCbeta function cell autonomously within the intestine to affect the activity of the p38 MAPK pathway, an important component of Caenorhabditis elegans immune and oxidative stress response. p38 MAPK activity in the intestine is regulated by diacylglycerol levels, a product of PLCbeta's hydrolytic activity. We provide genetic evidence that life span is largely determined by IIS, whereas p38 MAPK signaling is the primary regulator of oxidative stress in PLCbeta mutants. Pathogen sensitivity of Gqalpha and PLCbeta mutants is a summation of the beneficial effects of decreased IIS through reduced neuronal secretion and the detrimental effects of reduced activity of intestinal p38 MAPK. We propose a model whereby Gqalpha signaling differentially regulates pathogen sensitivity, oxidative stress, and longevity through cell autonomous and noncell autonomous effects on p38 MAPK and insulin/IGF1 signaling, respectively.
Kawli
Trupti
T
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Wu
Clay
C
Tan
Man-Wah
MW
D000818:Animals; D017173:Caenorhabditis elegans / Q000276:immunology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000276:immunology / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D008136:Longevity; D018384:Oxidative Stress; D054799:Phospholipase C beta / Q000378:metabolism; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D004075:Diglycerides; D044385:GTP-Binding Protein alpha Subunits; D054799:Phospholipase C beta