RRC ID 59589
Author Schulz A, Sekine Y, Oyeyemi MJ, Abrams AJ, Basavaraju M, Han SM, Groth M, Morrison H, Strittmatter SM, Hammarlund M.
Title The stress-responsive gene GDPGP1/mcp-1 regulates neuronal glycogen metabolism and survival.
Journal 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.
Volume 219(2)
Published 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
Times Cited 3
C.elegans tm5211 tm2679