Encoding and transducing the synaptic or extrasynaptic origin of NMDA receptor signals to the nucleus.
Cell
; 152(5): 1119-33, 2013 Feb 28.
Article
em En
| MEDLINE
| ID: mdl-23452857
ABSTRACT
The activation of N-methyl-D-aspartate-receptors (NMDARs) in synapses provides plasticity and cell survival signals, whereas NMDARs residing in the neuronal membrane outside synapses trigger neurodegeneration. At present, it is unclear how these opposing signals are transduced to and discriminated by the nucleus. In this study, we demonstrate that Jacob is a protein messenger that encodes the origin of synaptic versus extrasynaptic NMDAR signals and delivers them to the nucleus. Exclusively synaptic, but not extrasynaptic, NMDAR activation induces phosphorylation of Jacob at serine-180 by ERK1/2. Long-distance trafficking of Jacob from synaptic, but not extrasynaptic, sites depends on ERK activity, and association with fragments of the intermediate filament α-internexin hinders dephosphorylation of the Jacob/ERK complex during nuclear transit. In the nucleus, the phosphorylation state of Jacob determines whether it induces cell death or promotes cell survival and enhances synaptic plasticity.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Núcleo Celular
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Receptores de N-Metil-D-Aspartato
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Proteínas do Tecido Nervoso
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Cell
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Alemanha