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Full-Text Articles in Medicine and Health Sciences
Tyrosine 140 Of The Γ-Aminobutyric Acid Transporter Gat-1 Plays A Critical Role In Neurotransmitter Recognition, Yona Bismuth, Michael Kavanaugh, Baruch I. Kanner
Tyrosine 140 Of The Γ-Aminobutyric Acid Transporter Gat-1 Plays A Critical Role In Neurotransmitter Recognition, Yona Bismuth, Michael Kavanaugh, Baruch I. Kanner
Biomedical and Pharmaceutical Sciences Faculty Publications
The γ-aminobutyric acid (GABA) transporter GAT-1 is located in nerve terminals and catalyzes the electrogenic reuptake of the neurotransmitter with two sodium ions and one chloride. We now identify a single tyrosine residue that is critical for GABA recognition and transport. It is completely conserved throughout the superfamily, and even substitution to the other aromatic amino acids, phenylalanine (Y140F) and tryptophan (Y140W), results in completely inactive transporters. Electrophysiological characterization reveals that both mutant transporters exhibit the sodium-dependent transient currents associated with sodium binding as well as the chloride-dependent lithium leak currents characteristic of GAT-1. On the other hand, in both …
Mutation Of An Amino Acid Residue Influencing Potassium Coupling In The Glutamate Transporter Glt-1 Induces Obligate Exchange, Michael Kavanaugh, Annie Bendahan, Noa Zerangue, Yumin Zhang, Baruch I. Kanner
Mutation Of An Amino Acid Residue Influencing Potassium Coupling In The Glutamate Transporter Glt-1 Induces Obligate Exchange, Michael Kavanaugh, Annie Bendahan, Noa Zerangue, Yumin Zhang, Baruch I. Kanner
Biomedical and Pharmaceutical Sciences Faculty Publications
Glutamate transporters maintain low synaptic concentrations of neurotransmitter by coupling uptake to flux of other ions. After cotransport of glutamic acid with Na+, the cycle is completed by countertransport of K+. We have identified an amino acid residue (glutamate 404) influencing ion coupling in a domain of the transporter implicated previously in kainate binding. Mutation of this residue to aspartate (E404D) prevents both forward and reverse transport induced by K+. Sodium-dependent transmitter exchange and a transporter-mediated chloride conductance are unaffected by the mutation, indicating that this residue selectively influences potassium flux coupling. The results …
Excitatory Amino Acid Transporter 5, A Retinal Glutamate Transporter Coupled To A Chloride Conductance, Jeffrey L. Arriza, Scott Eliasof, Michael Kavanaugh, Susan G. Amara
Excitatory Amino Acid Transporter 5, A Retinal Glutamate Transporter Coupled To A Chloride Conductance, Jeffrey L. Arriza, Scott Eliasof, Michael Kavanaugh, Susan G. Amara
Biomedical and Pharmaceutical Sciences Faculty Publications
Although a glutamate-gated chloride conductance with the properties of a sodium-dependent glutamate transporter has been described in vertebrate retinal photoreceptors and bipolar cells, the molecular species underlying this conductance has not yet been identified. We now report the cloning and functional characterization of a human excitatory amino acid transporter, EAAT5, expressed primarily in retina. Although EAAT5 shares the structural homologies of the EAAT gene family, one novel feature of the EAAT5 sequence is a carboxy-terminal motif identified previously in N-methyl-d-aspartate receptors and potassium channels and shown to confer interactions with a family of synaptic proteins that promote ion channel …
Multiple Ionic Conductances Of The Human Dopamine Transporter: The Actions Of Dopamine And Psychostimulants, Mark S. Sonders, Si-Jia Zhu, Nancy R. Zahniser, Michael Kavanaugh, Susan G. Amara
Multiple Ionic Conductances Of The Human Dopamine Transporter: The Actions Of Dopamine And Psychostimulants, Mark S. Sonders, Si-Jia Zhu, Nancy R. Zahniser, Michael Kavanaugh, Susan G. Amara
Biomedical and Pharmaceutical Sciences Faculty Publications
Electrophysiological and pharmacological studies of a cloned human dopamine transporter (hDAT) were undertaken to investigate the mechanisms of transporter function and the actions of drugs at this target. Using two-electrode voltage-clamp techniques with hDAT-expressing Xenopus laevis oocytes, we show that hDAT can be considered electrogenic by two criteria. (1) Uptake of hDAT substrates gives rise to a pharmacologically appropriate “transport-associated” current. (2) The velocity of DA uptake measured in oocytes clamped at various membrane potentials was voltage-dependent, increasing with hyperpolarization. Concurrent measurement of transport-associated current and substrate flux in individual oocytes revealed that charge movement during substrate translocation was greater …
Aspartate 19 And Glutamate 121 Are Critical For Transport Function Of The Myo-Inositol/H+ Symporter From Leishmania Donovani, Andreas Seyfang, Michael Kavanaugh, Scott M. Landfear
Aspartate 19 And Glutamate 121 Are Critical For Transport Function Of The Myo-Inositol/H+ Symporter From Leishmania Donovani, Andreas Seyfang, Michael Kavanaugh, Scott M. Landfear
Biomedical and Pharmaceutical Sciences Faculty Publications
The protozoan flagellate Leishmania donovani has an active myo-inositol/proton symporter (MIT), which is driven by a proton gradient across the parasite membrane. We have used site-directed mutagenesis in combination with functional expression of transporter mutants in Xenopusoocytes and overexpression in Leishmania transfectants to investigate the significance of acidic transmembrane residues for proton relay and inositol transport. MIT has only three charged amino acids within predicted transmembrane domains. Two of these residues, Asp19 (TM1) and Glu121 (TM4), appeared to be critical for transport function of MIT, with a reduction of inositol transport to about 2% of wild-type …