Small-scale molecular motions accomplish glutamate uptake in human glutamate transporters

Hans P. Koch, Hans P Larsson

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Glutamate transporters remove glutamate from the synaptic deft to maintain efficient synaptic communication between neurons and to prevent glutamate concentrations from reaching neurotoxic levels. Glutamate transporters play an important role in ischemic neuronal death during stroke and have been implicated in epilepsy and amytropic lateral sclerosis. However, the molecular structure and the glutamate-uptake mechanism of these transporters are not well understood. The most recent models of glutamate transporters have three or five subunits, each with eight transmembrane domains, and one or two membrane-inserted loops. Here, using fluorescence resonance energy transfer (FRET) analysis, we have determined the relative position of the extracellular regions of these domains. Our results are consistent with a trimeric glutamate transporter with a large (>45 Å) extracellular vestibule. In contrast to other transport proteins, our FRET measurements indicate that there are no large-scale motions in glutamate transporters and that glutamate uptake is accompanied by relatively small motions around the glutamate-binding sites. The large extracellular vestibule and the small-scale conformational changes could contribute to the fast kinetics predicted for glutamate transporters. Furthermore, we show that, despite the multimeric nature of glutamate transporters, the subunits function independently.

Original languageEnglish
Pages (from-to)1730-1736
Number of pages7
JournalJournal of Neuroscience
Volume25
Issue number7
DOIs
StatePublished - Feb 16 2005
Externally publishedYes

Fingerprint

Amino Acid Transport System X-AG
Glutamic Acid
Fluorescence Resonance Energy Transfer
Motor Neuron Disease
Molecular Structure
Epilepsy
Carrier Proteins
Stroke
Binding Sites
Communication
Neurons
Membranes

Keywords

  • EAAT3
  • Fluorescence
  • FRET
  • Independence
  • Trimer
  • Uptake mechanism

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Small-scale molecular motions accomplish glutamate uptake in human glutamate transporters. / Koch, Hans P.; Larsson, Hans P.

In: Journal of Neuroscience, Vol. 25, No. 7, 16.02.2005, p. 1730-1736.

Research output: Contribution to journalArticle

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