RRC ID 46621
Author Kawli T, Wu C, Tan MW.
Title Systemic and cell intrinsic roles of Gqalpha signaling in the regulation of innate immunity, oxidative stress, and longevity in Caenorhabditis elegans.
Journal Proc Natl Acad Sci U S A
Abstract 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.
Volume 107(31)
Pages 13788-93
Published 2010-8-3
DOI 10.1073/pnas.0914715107
PII 0914715107
PMID 20647387
PMC PMC2922217
MeSH Animals Caenorhabditis elegans / immunology Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / immunology Caenorhabditis elegans Proteins / metabolism* Diglycerides / metabolism GTP-Binding Protein alpha Subunits / genetics GTP-Binding Protein alpha Subunits / immunology GTP-Binding Protein alpha Subunits / metabolism* Gene Expression Regulation Immunity, Innate* Longevity* Oxidative Stress* Phospholipase C beta / metabolism Signal Transduction*
IF 9.412
Times Cited 28
C.elegans tm1907