The p38 MAP kinase pathway modulates the hypoxia response and glutamate receptor trafficking in aging neurons.
Elife
; 52016 Jan 05.
Article
em En
| MEDLINE
| ID: mdl-26731517
ABSTRACT
Neurons are sensitive to low oxygen (hypoxia) and employ a conserved pathway to combat its effects. Here, we show that p38 MAP Kinase (MAPK) modulates this hypoxia response pathway in C. elegans. Mutants lacking p38 MAPK components pmk-1 or sek-1 resemble mutants lacking the hypoxia response component and prolyl hydroxylase egl-9, with impaired subcellular localization of Mint orthologue LIN-10, internalization of glutamate receptor GLR-1, and depression of GLR-1-mediated behaviors. Loss of p38 MAPK impairs EGL-9 protein localization in neurons and activates the hypoxia-inducible transcription factor HIF-1, suggesting that p38 MAPK inhibits the hypoxia response pathway through EGL-9. As animals age, p38 MAPK levels decrease, resulting in GLR-1 internalization; this age-dependent downregulation can be prevented through either p38 MAPK overexpression or removal of CDK-5, an antagonizing kinase. Our findings demonstrate that p38 MAPK inhibits the hypoxia response pathway and determines how aging neurons respond to hypoxia through a novel mechanism.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Hipóxia Celular
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Receptores de Glutamato
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Caenorhabditis elegans
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Sistema de Sinalização das MAP Quinases
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Proteínas de Caenorhabditis elegans
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Proteínas Quinases p38 Ativadas por Mitógeno
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Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article