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5 - Glutamate transporters

from Part I - Basic aspects of neurodegeneration

Published online by Cambridge University Press:  04 August 2010

M. Flint Beal ,
Anthony E. Lang  and
Albert C. Ludolph
By
Davide Trotti  and
Stuart L. Gibb
M. Flint Beal
Affiliation:
Cornell University, New York
Anthony E. Lang
Affiliation:
University of Toronto
Albert C. Ludolph
Affiliation:
Universität Ulm, Germany
Davide Trotti
Affiliation:
Department of Neurology, Massachusetts General Hospital Harvard Medical School, Charlestown, MS, USA
Stuart L. Gibb
Affiliation:
Massachusetts General Hospital Harvard Medical School, Charlestown, MS, USA
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Summary

Introduction

In the central nervous system (CNS) of mammals, glutamate acts as a chemical transmitter of excitatory signals by binding to different glutamate receptors and activating a multitude of highly integrated molecular pathways. Termination of this excitatory neurotransmission occurs via re-uptake of glutamate by specialized high affinity transporters capable of maintaining glutamate at ∼1 μM levels in the synaptic cleft. At higher concentrations, glutamate can also act as neurotoxin causing degeneration and death of neurons (Choi, 1992). This event is known as excitotoxicity and contributes to many chronic and acute neurodegenerative diseases. Therefore, glutamate homeostasis and the regulation of glutamate transporter abundance and function are a key element for the normal brain function.

High affinity, Na+-dependent glutamate transporters: localization, functional properties and topology

Molecular cloning has identified five different subtypes of Na+-dependent glutamate transporters, termed EAAT1–5 (excitatory amino acid transporters 1–5; nomenclature used for human subtypes). At present, two different nomenclatures are in use in the literature to indicate human and rodent isoforms (Table 5.1). However, the homologues show a high degree of interspecies conservation (>95%) and do not differ functionally. The gene names for the human transporter are as follows: EAAT3 or SLC1A1; EAAT2 or SLC1A2; EAAT1 or SLC1A3; EAAT4 or SLC1A4; EAAT5 or SLC1A5. The acronym SLC1 refers to ‘Solute Carrier family’ number 1 and A1 to family member number 1.

Localization

Immunohistochemistry studies revealed that the glutamate transporters EAAT1 and EAAT2 are localized to astroglial membranes that immediately oppose synaptic cleft regions of the neuropil.

Type
Chapter
Information
Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
 , pp. 57 - 64
Publisher: Cambridge University Press
Print publication year: 2005

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  • Glutamate transporters
    • By Davide Trotti, Department of Neurology, Massachusetts General Hospital Harvard Medical School, Charlestown, MS, USA, Stuart L. Gibb, Massachusetts General Hospital Harvard Medical School, Charlestown, MS, USA
  • M. Flint Beal, Cornell University, New York, Anthony E. Lang, University of Toronto, Albert C. Ludolph, Universität Ulm, Germany
  • Book: Neurodegenerative Diseases
  • Online publication: 04 August 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511544873.006
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  • Glutamate transporters
    • By Davide Trotti, Department of Neurology, Massachusetts General Hospital Harvard Medical School, Charlestown, MS, USA, Stuart L. Gibb, Massachusetts General Hospital Harvard Medical School, Charlestown, MS, USA
  • M. Flint Beal, Cornell University, New York, Anthony E. Lang, University of Toronto, Albert C. Ludolph, Universität Ulm, Germany
  • Book: Neurodegenerative Diseases
  • Online publication: 04 August 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511544873.006
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  • Glutamate transporters
    • By Davide Trotti, Department of Neurology, Massachusetts General Hospital Harvard Medical School, Charlestown, MS, USA, Stuart L. Gibb, Massachusetts General Hospital Harvard Medical School, Charlestown, MS, USA
  • M. Flint Beal, Cornell University, New York, Anthony E. Lang, University of Toronto, Albert C. Ludolph, Universität Ulm, Germany
  • Book: Neurodegenerative Diseases
  • Online publication: 04 August 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511544873.006
Available formats
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