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 Citations (Scopus)

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 2012

Fingerprint

Sirolimus
Glutamic Acid
Down-Regulation
N-Methyl-D-Aspartate Receptors
Proteasome Endopeptidase Complex
Proteins
GTPase-Activating Proteins
Proteasome Inhibitors
Tuberous Sclerosis
Proteolysis
tuberous sclerosis complex 2 protein
Neurons

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

A role of the mammalian target of rapamycin (mTOR) in glutamate-induced down-regulation of tuberous sclerosis complex proteins 2 (TSC2). / Ru, Wenjuan; Peng, Yanxi; Zhong, Ling; Tang, Shao-Jun.

In: Journal of Molecular Neuroscience, Vol. 47, No. 2, 06.2012, p. 340-345.

Research output: Contribution to journalArticle

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