RRC ID 75967
Author He B, Xu J, Pang S, Tang H.
Title Phosphatidylcholine mediates the crosstalk between LET-607 and DAF-16 stress response pathways.
Journal PLoS Genet
Abstract Coordinated regulation of stress response pathways is crucial for cellular homeostasis. However, crosstalk between the different stress pathways and the physiological significance of this crosstalk remain poorly understood. In this study, using the model organism C. elegans, we discovered that suppression of the transcription factor LET-607/CREBH, a regulator of cellular defense and proteostatic responses, triggers adaptive induction of DAF-16-dependent stress responses. Suppression of LET-607 improves stress resistance and extends C. elegans lifespan in a DAF-16-dependent manner. We identified the sphingomyelin synthase SMS-5 to be a central mediator in the communication between LET-607 and DAF-16. SMS-5 reduces the contents of unsaturated phosphatidylcholine (PC), which activates DAF-16 through ITR-1-dependent calcium signaling and calcium-sensitive kinase PKC-2. Our data reveal the significance of crosstalk between different stress pathways in animal fitness and identify LET-607/CREBH and specific PC as regulators of DAF-16 and longevity.
Volume 17(5)
Pages e1009573
Published 2021-5-1
DOI 10.1371/journal.pgen.1009573
PMID 34014977
PMC PMC8172019
MeSH Adaptation, Physiological Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Calcium Signaling Cyclic AMP Response Element-Binding Protein / metabolism* Forkhead Transcription Factors / metabolism* Germ-Line Mutation Longevity / genetics Membrane Lipids / metabolism Nerve Tissue Proteins / metabolism* Phosphatidylcholines / metabolism* Protein Kinase C / metabolism Stress, Physiological* Transferases (Other Substituted Phosphate Groups) / genetics Transferases (Other Substituted Phosphate Groups) / metabolism*
C.elegans tm1452