Systemic and cell intrinsic roles of Gqalpha signaling in the regulation of innate immunity, oxidative stress, and longevity in Caenorhabditis elegans.

Proceedings of the National Academy of Sciences of the United States of America
Trupti KawliMan-Wah Tan

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 ...Continue Reading

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Citations

Mar 29, 2012·BMC Microbiology·Cynthia Portal-CelhayMartin J Blaser
Jan 18, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yuqi QinYun Zhang
Aug 13, 2014·Proceedings of the National Academy of Sciences of the United States of America·Cheng-Gang ZouKe-Qin Zhang
Sep 24, 2013·Worm·Alexandra Anderson, Rachel McMullan
Jul 1, 2012·Worm·Ransome van der HoevenDanielle A Garsin
Sep 29, 2011·Developmental and Comparative Immunology·Jun WangHinrich Schulenburg
Jan 13, 2012·Current Opinion in Immunology·Read Pukkila-Worley, Frederick M Ausubel
Feb 1, 2011·Cellular Microbiology·Man-Wah Tan, Michael Shapira
Nov 5, 2016·The Journal of Experimental Medicine·Brooke A NapierDenise M Monack
Nov 11, 2016·PLoS Pathogens·Katie C McCallum, Danielle A Garsin
Jun 6, 2016·Biochemical Pharmacology·Jerome Reboul, Jonathan J Ewbank
Jul 2, 2021·Aging Cell·Seungjin RyuYousin Suh
Nov 22, 2011·Current Biology : CB·Suhong Xu, Andrew D Chisholm

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