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.
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Acknowledgements
This work was supported by the UTMB start-up funds and a grant from the TS Alliance to S.-J.T., and grants from the National Natural Science Foundation of China (No. 30873457) and the Scientific Technology Project of Guangdong Province of China (No.2008A060202010 and No. 2010B050700019) to L.Z.
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W. Ru and Y. Peng contribute equally to this work.
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Ru, W., Peng, Y., Zhong, L. et al. 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, 340–345 (2012). https://doi.org/10.1007/s12031-012-9753-1
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DOI: https://doi.org/10.1007/s12031-012-9753-1