PMID- 22483750
OWN - NLM
STAT- MEDLINE
DCOM- 20120709
LR  - 20211203
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 421
IP  - 2
DP  - 2012 May 4
TI  - Regulation of the glutamate transporter EAAT3 by mammalian target of rapamycin 
      mTOR.
PG  - 159-63
LID - 10.1016/j.bbrc.2012.03.109 [doi]
AB  - The serine/threonine kinase mammalian target of rapamycin (mTOR) is stimulated by 
      insulin, growth factors and nutrients and confers survival of several cell types. 
      The kinase has previously been shown to stimulate amino acid uptake. In neurons, 
      the cellular uptake of glutamate by the excitatory amino-acid transporters 
      (EAATs) decreases excitation and thus confers protection against excitotoxicity. 
      In epithelia, EAAT3 accomplishes transepithelial glutamate and aspartate 
      transport. The present study explored, whether mTOR regulates EAAT3 (SLC1A1). To 
      this end, cRNA encoding EAAT3 was injected into Xenopus oocytes with or without 
      cRNA encoding mTOR and the glutamate induced current (I(glu)), a measure of 
      glutamate transport, determined by dual electrode voltage clamp. Moreover, EAAT3 
      protein abundance was determined utilizing chemiluminescence. As a result, I(glu) 
      was observed in Xenopus oocytes expressing EAAT3 but not in water injected 
      oocytes. Coexpression of mTOR significantly increased I(glu), an effect reversed 
      by rapamycin (100 nM). mTOR coexpression increased EAAT3 protein abundance in the 
      cell membrane. The decay of I(glu) following inhibition of carrier insertion with 
      brefeldin A in oocytes coexpressing EAAT3 with mTOR was similar in the presence 
      and absence of rapamycin (100 nM). In conclusion, mTOR is a novel powerful 
      regulator of EAAT3 and may thus contribute to protection against 
      neuroexcitotoxicity.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Almilaji, Ahmad
AU  - Almilaji A
AD  - Department of Physiology, University of Tubingen, Gmelinstr. 5, D-72076 Tubingen, 
      Germany.
FAU - Pakladok, Tatsiana
AU  - Pakladok T
FAU - Guo, Anne
AU  - Guo A
FAU - Munoz, Carlos
AU  - Munoz C
FAU - Foller, Michael
AU  - Foller M
FAU - Lang, Florian
AU  - Lang F
LA  - eng
PT  - Journal Article
DEP - 20120329
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Excitatory Amino Acid Transporter 3)
RN  - 0 (SLC1A1 protein, human)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Excitatory Amino Acid Transporter 3/*biosynthesis/genetics
MH  - Glutamic Acid/*metabolism
MH  - Humans
MH  - Oocytes
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Xenopus
EDAT- 2012/04/10 06:00
MHDA- 2012/07/10 06:00
CRDT- 2012/04/10 06:00
PHST- 2012/03/20 00:00 [received]
PHST- 2012/03/21 00:00 [accepted]
PHST- 2012/04/10 06:00 [entrez]
PHST- 2012/04/10 06:00 [pubmed]
PHST- 2012/07/10 06:00 [medline]
AID - S0006-291X(12)00578-5 [pii]
AID - 10.1016/j.bbrc.2012.03.109 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2012 May 4;421(2):159-63. doi: 
      10.1016/j.bbrc.2012.03.109. Epub 2012 Mar 29.