A role of the mammalian target of rapamycin (mTOR) in glutamate-induced down-regulation of tuberous sclerosis complex proteins 2 (TSC2)

Wenjuan Ru, Yanxi Peng, Ling Zhong, Shao Jun Tang

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)340-345
Number of pages6
JournalJournal of Molecular Neuroscience
Volume47
Issue number2
DOIs
StatePublished - Jun 1 2012

    Fingerprint

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this