title: The importance of the excitatory amino acid transporter 3 (EAAT3).
abstract: The neuronal excitatory amino acid transporter 3 (EAAT3) is fairly ubiquitously expressed in the brain, though it does not necessarily maintain the same function everywhere. It is important in maintaining low local concentrations of glutamate, where its predominant post-synaptic localization can buffer nearby glutamate receptors and modulate excitatory neurotransmission and synaptic plasticity. It is also the main neuronal cysteine uptake system acting as the rate-limiting factor for the synthesis of glutathione, a potent antioxidant, in EAAT3 expressing neurons, while on GABAergic neurons, it is important in supplying glutamate as a precursor for GABA synthesis. Several diseases implicate EAAT3, and modulation of this transporter could prove a useful therapeutic approach. Regulation of EAAT3 could be targeted at several points for functional modulation, including the level of transcription, trafficking and direct pharmacological modulation, and indeed, compounds and experimental treatments have been identified that regulate EAAT3 function at different stages, which together with observations of EAAT3 regulation in patients is giving us insight into the endogenous function of this transporter, as well as the consequences of altered function. This review summarizes work done on elucidating the role and regulation of EAAT3.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 København Ø, Denmark.
authors.forename: Walden E
authors.initials: WE
authors.lastname: Bjørn-Yoshimoto
authors.affiliation: National Institute of Mental Health, National Institutes of Health, 35 Convent Drive Room 3A: 210 MSC3742, Bethesda, MD 20892-3742, USA. Electronic address: smunderhill@yahoo.com.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Underhill
mesh_terms: D000818:Animals; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D001523:Mental Disorders / Q000235:genetics / Q000378:metabolism; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D050580:Excitatory Amino Acid Transporter 3; C493400:SLC1A1 protein, human; D005680:gamma-Aminobutyric Acid
keywords: EAAT3; Glutamate transporter