title: Glutamate transporter type 3 regulates mouse hippocampal GluR1 trafficking.
abstract: BACKGROUND
  Rapid trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) to the plasma membrane is considered a fundamental biological process for learning and memory. GluR1 is an AMPAR subunit. We have shown that mice with knockout of excitatory amino acid transporter type 3 (EAAT3), a neuronal glutamate transporter, have impaired learning and memory. The mechanisms for this impairment are not known and may be via regulation of AMPAR trafficking.
  
  
  METHODS
  Freshly prepared 300μm coronal hippocampal slices from wild-type or EAAT3 knockout mice were incubated with or without 25mM tetraethylammonium for 10min. The trafficking of GluR1, an AMPAR subunit, to the plasma membrane and its phosphorylation were measured.
  
  
  RESULTS
  Tetraethylammonium increased the trafficking of GluR1 and EAAT3 to the plasma membrane in the wild-type mouse hippocampal slices but did not cause GluR1 trafficking in the EAAT3 knockout mice. Tetraethylammonium also increased the phosphorylation of GluR1 at S845, a protein kinase A (PKA) site, in the wild-type mice but not in the EAAT3 knockout mice. The PKA antagonist KT5720 attenuated tetraethylammonium-induced GluR1 phosphorylation and trafficking in the wild-type mice. The PKA agonist 6-BNz-cAMP caused GluR1 trafficking to the plasma membrane in the EAAT3 knockout mice. In addition, EAAT3 was co-immunoprecipitated with PKA.
  
  
  CONCLUSIONS
  These results suggest that EAAT3 is upstream of PKA in a pathway to regulate GluR1 trafficking.
  
  
  CONCLUSIONS
  Our results provide initial evidence for the involvement of EAAT3 in the biochemical cascade of learning and memory.
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA 22903, USA; Department of Anesthesiology and Operation Center, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Jiangbei
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA 22903, USA; Department of Anesthesiology, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Anesthesiology and Operation Center, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Mi
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA 22903, USA. Electronic address: zz3c@virginia.edu.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D050580:Excitatory Amino Acid Transporter 3 / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; D050580:Excitatory Amino Acid Transporter 3; D018091:Receptors, AMPA; D013757:Tetraethylammonium Compounds; C493399:Slc1a1 protein, mouse
keywords: GluR1; Glutamate transporters type 3; Mice; Trafficking; α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionicacid receptor