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 language | English |
|---|---|
| Pages (from-to) | 1730-1736 |
| Number of pages | 7 |
| Journal | Journal of Neuroscience |
| Volume | 25 |
| Issue number | 7 |
| DOIs | |
| State | Published - Feb 16 2005 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Small-scale molecular motions accomplish glutamate uptake in human glutamate transporters
AU - Koch, Hans P.
AU - Larsson, Hans P
PY - 2005/2/16
Y1 - 2005/2/16
N2 - 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.
AB - 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.
KW - EAAT3
KW - Fluorescence
KW - FRET
KW - Independence
KW - Trimer
KW - Uptake mechanism
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U2 - 10.1523/JNEUROSCI.4138-04.2005
DO - 10.1523/JNEUROSCI.4138-04.2005
M3 - Article
VL - 25
SP - 1730
EP - 1736
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 7
ER -