Phosphatidylcholine mediates the crosstalk between LET-607 and DAF-16 stress response pathways.
PLoS Genet
; 17(5): e1009573, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-34014977
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatidilcolinas
/
Estresse Fisiológico
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
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Caenorhabditis elegans
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Transferases (Outros Grupos de Fosfato Substituídos)
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Proteínas de Caenorhabditis elegans
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Fatores de Transcrição Forkhead
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Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article