Journal
JOURNAL OF MOLECULAR NEUROSCIENCE
Volume 47, Issue 2, Pages 340-345Publisher
HUMANA PRESS INC
DOI: 10.1007/s12031-012-9753-1
Keywords
mTOR; TSC2; Rapamycin; NMDA receptor; Tuberous sclerosis complex; Synaptic activity
Categories
Funding
- UTMB
- TS Alliance
- National Natural Science Foundation of China [30873457]
- Scientific Technology Project of Guangdong Province of China [2008A060202010, 2010B050700019]
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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.
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