| RRC ID |
85012
|
| 著者 |
Maman M, Carvalhal Marques F, Volovik Y, Dubnikov T, Bejerano-Sagie M, Cohen E.
|
| タイトル |
A neuronal GPCR is critical for the induction of the heat shock response in the nematode C. elegans.
|
| ジャーナル |
J Neurosci
|
| Abstract |
In the nematode Caenorhabditis elegans, the heat shock response (HSR) is regulated at the organismal level by a network of thermosensory neurons that senses elevated temperatures and activates the HSR in remote tissues. Which neuronal receptors are required for this signaling mechanism and in which neurons they function are largely unanswered questions. Here we used worms that were engineered to exhibit RNA interference hypersensitivity in neurons to screen for neuronal receptors that are required for the activation of the HSR and identified a putative G-protein coupled receptor (GPCR) as a novel key component of this mechanism. This gene, which we termed GPCR thermal receptor 1 (gtr-1), is expressed in chemosensory neurons and has no role in heat sensing but is critically required for the induction of genes that encode heat shock proteins in non-neural tissues upon exposure to heat. Surprisingly, the knock-down of gtr-1 by RNA interference protected worms expressing the Alzheimer's-disease-linked aggregative peptide Aβ3-42 from proteotoxicity but had no effect on lifespan. This study provides several novel insights: (1) it shows that chemosensory neurons play important roles in the nematode's HSR-regulating mechanism, (2) it shows that lifespan and heat stress resistance are separable, and (3) it strengthens the emerging notion that the ability to respond to heat comes at the expense of protein homeostasis (proteostasis).
|
| 巻・号 |
33(14)
|
| ページ |
6102-11
|
| 公開日 |
2013-4-3
|
| DOI |
10.1523/JNEUROSCI.4023-12.2013
|
| PII |
33/14/6102
|
| PMID |
23554491
|
| PMC |
PMC6618909
|
| MeSH |
Amyloid beta-Peptides / metabolism
Animals
Animals, Genetically Modified
Bacterial Infections / prevention & control
Caenorhabditis elegans
Caenorhabditis elegans Proteins / genetics
Eggs
Gene Expression Regulation / genetics
Gene Expression Regulation / physiology*
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Heat-Shock Proteins / genetics
Heat-Shock Proteins / metabolism
Heat-Shock Response / genetics
Heat-Shock Response / physiology*
Hot Temperature*
Muscles / metabolism
Mutation / genetics
Neurons / metabolism*
Paralysis / genetics
Peptide Fragments / metabolism
Plant Lectins / genetics
Plant Lectins / metabolism
RNA Interference
RNA, Messenger / genetics
Receptors, G-Protein-Coupled / genetics
Receptors, G-Protein-Coupled / metabolism*
Sexual Behavior, Animal
Signal Transduction / genetics
Signal Transduction / physiology
Stress, Physiological / genetics
Stress, Physiological / physiology
Thermosensing / genetics
Thermosensing / physiology*
Transcription Factors / genetics
Transcription Factors / metabolism
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| リソース情報 |
| 線虫 |
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