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.
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.
Huang
Yunfei
Y
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
Kang
Bingnan N
BN
Tian
Jing
J
Liu
Yi
Y
Luo
Hongbo R
HR
Hester
Lynda
L
Snyder
Solomon H
SH
D026923:Amino Acid Transport Systems, Basic / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D050916:TRPV Cation Channels / Q000378:metabolism*
D026923:Amino Acid Transport Systems, Basic; D016194:Receptors, N-Methyl-D-Aspartate; C105348:Slc7a3 protein, rat; D050916:TRPV Cation Channels; C120776:TRPV6 channel; D001120:Arginine; D011494:Protein Kinases; C546842:MTOR protein, human; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases