title: Molecular physiology of EAAT anion channels.
abstract: Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. After release from presynaptic nerve terminals, glutamate is quickly removed from the synaptic cleft by a family of five glutamate transporters, the so-called excitatory amino acid transporters (EAAT1-5). EAATs are prototypic members of the growing number of dual-function transport proteins: they are not only glutamate transporters, but also anion channels. Whereas the mechanisms underlying secondary active glutamate transport are well understood at the functional and at the structural level, mechanisms and cellular roles of EAAT anion conduction have remained elusive for many years. Recently, molecular dynamics simulations combined with simulation-guided mutagenesis and experimental analysis identified a novel anion-conducting conformation, which accounts for all experimental data on EAAT anion currents reported so far. We here review recent findings on how EAATs accommodate a transporter and a channel in one single protein.
authors.affiliation: Institute of Complex Systems, Zelluläre Biophysik (ICS-4), Forschungszentrum Jülich, 52425, Jülich, Germany. c.fahlke@fz-juelich.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Fahlke
authors.affiliation: Institute of Complex Systems, Zelluläre Biophysik (ICS-4), Forschungszentrum Jülich, 52425, Jülich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kortzak
authors.affiliation: Institute of Complex Systems, Zelluläre Biophysik (ICS-4), Forschungszentrum Jülich, 52425, Jülich, Germany.
authors.forename: Jan-Philipp
authors.initials: JP
authors.lastname: Machtens
mesh_terms: D000818:Animals; D050491:Glutamate Plasma Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation
chemical_list: D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid
keywords: Anion channel; Computational electrophysiology; Glutamate transport; Molecular dynamics simulation