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Mechanism of chloride interaction with neurotransmitter:sodium symporters

Author

Listed:
  • Elia Zomot

    (Hebrew University Hadassah Medical School, POB 12272, Jerusalem 91120, Israel)

  • Annie Bendahan

    (Hebrew University Hadassah Medical School, POB 12272, Jerusalem 91120, Israel)

  • Matthias Quick

    (Center for Molecular Recognition and,
    New York State Psychiatric Institute, New York, New York 10032, USA)

  • Yongfang Zhao

    (Center for Molecular Recognition and,)

  • Jonathan A. Javitch

    (Center for Molecular Recognition and,
    Columbia University, 630 W. 168th, New York, New York 10032, USA
    New York State Psychiatric Institute, New York, New York 10032, USA)

  • Baruch I. Kanner

    (Hebrew University Hadassah Medical School, POB 12272, Jerusalem 91120, Israel)

Abstract

Neurotransmitter transport A landmark paper in structural biology recently documented the crystal structure of LeuT, a bacterial homologue of Na+/Cl−-dependent neurotransmitter transporters. In this homologue the transporter binds to two sodium ions and a substrate molecule. In the real neurotransmitter transporters of this family, chloride is co-transported with sodium and the neurotransmitter. Zomot et al. apply structural and mechanistic knowledge of LeuT, and a chloride transporter from an entirely different family, to mammalian neurotransmitter:sodium symporter (NSS) transporters, including GAT-1. They find that transported chloride ions serve to neutralize the positive charge carried by the sodium ions, and establish the probable location of the binding site for chloride, right next to one of the sodium ions. The mechanism of these transporters is of particular interest because of their role in the regulation of neurotransmission and as the site of action of drugs such as Prozac (fluoxetine).

Suggested Citation

  • Elia Zomot & Annie Bendahan & Matthias Quick & Yongfang Zhao & Jonathan A. Javitch & Baruch I. Kanner, 2007. "Mechanism of chloride interaction with neurotransmitter:sodium symporters," Nature, Nature, vol. 449(7163), pages 726-730, October.
    • Handle: RePEc:nat:nature:v:449:y:2007:i:7163:d:10.1038_nature06133
    DOI: 10.1038/nature06133
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    Cited by:

    1. Jufang Shan & Jonathan A Javitch & Lei Shi & Harel Weinstein, 2011. "The Substrate-Driven Transition to an Inward-Facing Conformation in the Functional Mechanism of the Dopamine Transporter," PLOS ONE, Public Library of Science, vol. 6(1), pages 1-15, January.
    2. Saher Afshan Shaikh & Emad Tajkhorshid, 2010. "Modeling and Dynamics of the Inward-Facing State of a Na+/Cl− Dependent Neurotransmitter Transporter Homologue," PLOS Computational Biology, Public Library of Science, vol. 6(8), pages 1-14, August.

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