Phosphatidylcholine mediates the crosstalk between LET-607 and DAF-16 stress response pathways

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 suppr...

Full description

Saved in:
Bibliographic Details
Published in:PLoS genetics 2021-05, Vol.17 (5), p.e1009573-e1009573
Main Authors: He, Bin, Xu, Jie, Pang, Shanshan, Tang, Haiqing
Format: Article
Language:English
Subjects:
Adaptation, Physiological
Animals
Biological control systems
Biology and life sciences
Caenorhabditis elegans - metabolism
Caenorhabditis elegans Proteins - metabolism
Calcium Signaling
Cellular stress response
Cyclic AMP Response Element-Binding Protein - metabolism
Defense
Forkhead Transcription Factors - metabolism
Germ-Line Mutation
Homeostasis
Kinases
Lecithin
Localization
Longevity - genetics
Mammals
Membrane Lipids - metabolism
Nerve Tissue Proteins - metabolism
Observations
Pathogens
Phosphatidylcholine
Phosphatidylcholines - metabolism
Physiological aspects
Protein Kinase C - metabolism
Proteins
Research and Analysis Methods
RNA-mediated interference
Stress (Physiology)
Stress, Physiological
Transcription factors
Transferases (Other Substituted Phosphate Groups) - genetics
Transferases (Other Substituted Phosphate Groups) - metabolism
Worms
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1009573