Genetic analysis of KillerRed in C. elegans identifies a shared role of calcium genes in ROS-mediated neurodegeneration.
Animals
Caenorhabditis elegans
Caenorhabditis elegans Proteins
/ genetics
Calcium
/ metabolism
Calreticulin
/ genetics
GABAergic Neurons
/ metabolism
Green Fluorescent Proteins
/ toxicity
Inositol 1,4,5-Trisphosphate Receptors
/ genetics
Nerve Degeneration
/ chemically induced
Reactive Oxygen Species
/ metabolism
Ryanodine Receptor Calcium Release Channel
/ genetics
None
calcium
neurodegeneration
reactive oxygen species
Journal
Journal of neurogenetics
ISSN: 1563-5260
Titre abrégé: J Neurogenet
Pays: England
ID NLM: 8406473
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
pubmed:
30
11
2018
medline:
23
6
2020
entrez:
30
11
2018
Statut:
ppublish
Résumé
In C. elegans, neurodegeneration induced by excitotoxicity or aggregation of misfolded proteins is dependent on genes involved in calcium release from the endoplasmic reticulum. Reactive oxygen species (ROS) can also induce neurodegeneration, but the relationship between ROS-mediated neurodegeneration and calcium has not been established. We activated KillerRed in the GABA neurons of C. elegans to produce ROS that leads to functional loss and structural degeneration of these neurons and demonstrated that the severity of neurodegeneration was dependent on extent of KillerRed activation. To genetically examine the role of calcium in ROS-mediated neurodegeneration, we measured functional neurodegeneration in itr-1 (inositol trisphosphate receptor), crt-1 (caltreticulin), and unc-68 (ryanodine receptor) mutants. Similar to other neurotoxic conditions, neurodegeneration triggered by KillerRed was reduced in itr-1 and crt-1 mutants. Somewhat unexpectedly, genetic or pharmacological disruption of unc-68 had a minimal effect on neurodegeneration. Our results indicate ROS-mediated neurodegeneration occurs through a conserved calcium regulated mechanism and suggest that components of the degeneration process have different sensitivities to ROS.
Identifiants
pubmed: 30489172
doi: 10.1080/01677063.2018.1531857
pmc: PMC6486406
mid: NIHMS1520197
doi:
Substances chimiques
CRT-1 protein, C elegans
0
Caenorhabditis elegans Proteins
0
Calreticulin
0
Inositol 1,4,5-Trisphosphate Receptors
0
Reactive Oxygen Species
0
Ryanodine Receptor Calcium Release Channel
0
Unc-68 protein, C elegans
0
killer red protein, Anthomedusae
0
Green Fluorescent Proteins
147336-22-9
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-9Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103499
Pays : United States
Organisme : NIH HHS
ID : P40 OD010440
Pays : United States
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