| RRC ID |
59589
|
| 著者 |
Schulz A, Sekine Y, Oyeyemi MJ, Abrams AJ, Basavaraju M, Han SM, Groth M, Morrison H, Strittmatter SM, Hammarlund M.
|
| タイトル |
The stress-responsive gene GDPGP1/mcp-1 regulates neuronal glycogen metabolism and survival.
|
| ジャーナル |
J Cell Biol
|
| Abstract |
Maladaptive responses to stress might play a role in the sensitivity of neurons to stress. To identify novel cellular responses to stress, we performed transcriptional analysis in acutely stressed mouse neurons, followed by functional characterization in Caenorhabditis elegans. In both contexts, we found that the gene GDPGP1/mcp-1 is down-regulated by a variety of stresses. Functionally, the enzyme GDPGP1/mcp-1 protects against stress. Knockdown of GDPGP1 in mouse neurons leads to widespread neuronal cell death. Loss of mcp-1, the single homologue of GDPGP1 in C. elegans, leads to increased degeneration of GABA neurons as well as reduced survival of animals following environmental stress. Overexpression of mcp-1 in neurons enhances survival under hypoxia and protects against neurodegeneration in a tauopathy model. GDPGP1/mcp-1 regulates neuronal glycogen levels, indicating a key role for this metabolite in neuronal stress resistance. Together, our data indicate that down-regulation of GDPGP1/mcp-1 and consequent loss of neuronal glycogen is a maladaptive response that limits neuronal stress resistance and reduces survival.
|
| 巻・号 |
219(2)
|
| 公開日 |
2020-2-3
|
| DOI |
10.1083/jcb.201807127
|
| PII |
133634
|
| PMID |
31968056
|
| PMC |
PMC7041677
|
| MeSH |
Animals
Apoptosis / genetics
Caenorhabditis elegans / genetics
Caenorhabditis elegans Proteins / genetics*
DNA Damage / genetics
Disease Models, Animal
Glucosyltransferases / genetics*
Glycogen / genetics
Glycogen / metabolism
Humans
Mice
Nerve Degeneration / genetics*
Nerve Degeneration / metabolism
Nerve Degeneration / pathology
Neurons / metabolism*
Neurons / pathology
|
| IF |
8.891
|
| 引用数 |
3
|
| リソース情報 |
| 線虫 |
tm5211
tm2679 |
