title: A role of the mammalian target of rapamycin (mTOR) in glutamate-induced down-regulation of tuberous sclerosis complex proteins 2 (TSC2).
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.
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Ru
authors.forename: Yanxi
authors.initials: Y
authors.lastname: Peng
authors.forename: Ling
authors.initials: L
authors.lastname: Zhong
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Tang
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D061251:Primary Cell Culture; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C000624654:Tsc2 protein, mouse; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D018698:Glutamic Acid; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex; D020123:Sirolimus