A role of the mammalian target of rapamycin (mTOR) in glutamate-induced down-regulation of tuberous sclerosis complex proteins 2 (TSC2).
J Mol Neurosci
; 47(2): 340-5, 2012 Jun.
Article
em En
| MEDLINE
| ID: mdl-22492229
ABSTRACT
Mammalian target of rapamycin (mTOR) signaling plays a critical role in the regulation of activity-dependent protein synthesis in neurons. It is well established that the GTPase-activating protein tuberous sclerosis complex proteins (2TSC2) is an upstream inhibitor of mTOR. In this study, we show that glutamate stimulation down-regulates TSC2 protein in cortical cultures via NMDA receptor (NMDAR) activation. Interestingly, the mTOR-specific inhibitor rapamycin blocks the glutamate-induced TSC2 down-regulation. This finding suggests that NMDAR activation evokes an mTOR-mediated negative regulation of TSC2. In addition, we also show that the glutamate-induced down-regulation of TSC2 protein is blocked by proteasome inhibitor MG132, indicating the involvement of proteasome-mediated protein degradation. We propose that the NMDAR activation stimulates an mTOR-proteasome pathway to degrade TSC2 protein.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação para Baixo
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Ácido Glutâmico
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Sirolimo
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Proteínas Supressoras de Tumor
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Serina-Treonina Quinases TOR
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Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article