A Role of the Mammalian Target of Rapamycin (mTOR) in Glutamate-Induced Down-regulation of Tuberous Sclerosis Complex Proteins 2 (TSC2)

作者：Ru, Wenjuan; Peng, Yanxi; Zhong, Ling; Tang, Shao Jun^*

来源：Journal of Molecular Neuroscience, 2012, 47(2): 340-345.

DOI：10.1007/s12031-012-9753-1

• mTOR
• TSC2
• Rapamycin
• NMDA receptor
• Tuberous sclerosis complex
• Synaptic activity

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.

• 出版日期2012-6
• 单位中山大学