title: Up-Regulation of Excitatory Amino Acid Transporters EAAT3 and EAAT4 by Lithium Sensitive Glycogen Synthase Kinase GSK3ß.
abstract: BACKGROUND
  Cellular uptake of glutamate by the excitatory amino-acid transporters (EAATs) decreases excitation and thus participates in the regulation of neuroexcitability. Kinases impacting on neuronal function include Lithium-sensitive glycogen synthase kinase GSK3ß. The present study thus explored whether the activities of EAAT3 and/or EAAT4 isoforms are sensitive to GSK3ß.
  
  
  METHODS
  cRNA encoding wild type EAAT3 (SLC1A1) or EAAT4 (SLC1A6) was injected into Xenopus oocytes without or with additional injection of cRNA encoding wild type GSK3ß or the inactive mutant K85AGSK3ß. Dual electrode voltage clamp was performed in order to determine glutamate-induced current (IEAAT).
  
  
  RESULTS
  Appreciable IEAAT was observed in EAAT3 or EAAT4 expressing but not in water injected oocytes. IEAAT was significantly increased by coexpression of GSK3ß but not by coexpression of K85AGSK3ß. Coexpression of GSK3ß increased significantly the maximal IEAAT in EAAT3 or EAAT4 expressing oocytes, without significantly modifying apparent affinity of the carriers. Lithium (1 mM) exposure for 24 hours decreased IEAAT in EAAT3 and GSK3ß expressing oocytes to values similar to IEAAT in oocytes expressing EAAT3 alone. Lithium did not significantly modify IEAAT in oocytes expressing EAAT3 without GSK3ß.
  
  
  CONCLUSIONS
  Lithium-sensitive GSK3ß is a powerful regulator of excitatory amino acid transporters EAAT3 and EAAT4.
authors.affiliation: Department of Cardiology, Vascular Medicine and Physiology I, University of Tuebingen, Tuebingen, Germany.
authors.forename: Abeer
authors.initials: A
authors.lastname: Abousaab
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism*; D050581:Excitatory Amino Acid Transporter 4 / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006801:Humans; D008094:Lithium / Q000494:pharmacology*; D050505:Mutant Proteins / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D014982:Xenopus laevis
chemical_list: D050580:Excitatory Amino Acid Transporter 3; D050581:Excitatory Amino Acid Transporter 4; D050505:Mutant Proteins; D018698:Glutamic Acid; D008094:Lithium; D000071679:Glycogen Synthase Kinase 3 beta