J Mol Neurosci 2012,
Ru, Wenjuan; Peng, Yanxi; Zhong, Ling; Tang, Shao-Jun
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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Text Mining Data
TSC2 → mammalian target of rapamycin (mTOR): " A role
of the mammalian target of rapamycin (mTOR)
in glutamate induced down-regulation of tuberous sclerosis complex proteins 2 ( TSC2
TSC2 ⊣ mTOR-specific: " Interestingly, the mTOR-specific inhibitor rapamycin blocks the glutamate induced TSC2 down-regulation "
TSC2 → mTOR: " This finding suggests that NMDAR activation evokes an mTOR mediated negative regulation of TSC2 "
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