The cationic amino acid transporters CAT1 and CAT3 mediate NMDA receptor activation-dependent changes in elaboration of neuronal processes via the mammalian target of rapamycin mTOR pathway

J Neurosci. 2007 Jan 17;27(3):449-58. doi: 10.1523/JNEUROSCI.4489-06.2007.

Abstract

Neuronal activity influences protein synthesis and neuronal growth. Availability of nutrients, especially leucine and arginine, regulates the mammalian target of rapamycin (mTOR) pathway that controls cell growth. We show that NMDA receptor activation markedly reduces arginine transport by decreasing surface expression of the cationic amino acid transporters (CAT) 1 and 3. Depletion of CAT1 and CAT3 by RNA interference blocks influences of NMDA receptor activation on the mTOR pathway and neuronal process formation. Thus, the CATs mediate influences of NMDA receptor activation on the mTOR pathway that regulates neuronal processes.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Transport Systems, Basic / metabolism*
  • Animals
  • Arginine / metabolism
  • Cell Line
  • Cells, Cultured
  • Humans
  • Neurons / metabolism*
  • Neurons / physiology
  • Protein Kinases / metabolism*
  • Rats
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases
  • TRPV Cation Channels / metabolism*

Substances

  • Amino Acid Transport Systems, Basic
  • Receptors, N-Methyl-D-Aspartate
  • Slc7a3 protein, rat
  • TRPV Cation Channels
  • TRPV6 channel
  • Arginine
  • Protein Kinases
  • MTOR protein, human
  • mTOR protein, rat
  • TOR Serine-Threonine Kinases