DOI: 10.1126/science.1097468. Vesicular Glutamate Transporters 1 and 2 Target to Functionally Distinct Synaptic Release Sites

Vesicular Glutamate Transporters 1 and 2 Target to Functionally Distinct Synaptic Release Sites

10.1126/science.1097468

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Vesicular glutamate transporters (VGLUTs) 1 and 2 show a mutually exclusive distribution in the adult brain that suggests specialization for synapses with different properties of release. Consistent with this distribution, inactivation of the VGLUT1 gene silenced a subset ofexcitatory neurons in the adult. However, the same cell populations exhibited VGLUT1-independent transmission early in life. Developing hippocampal neurons transiently coexpressed VGLUT2 and VGLUT1 at distinct synaptic sites with different short-term plasticity. The loss of VGLUT1 also reduced the reserve pool of synaptic vesicles. Thus, VGLUT1 plays an unanticipated role in membrane trafficking at the nerve terminal.

Bibliography

Fremeau, R. T., Kam, K., Qureshi, T., Johnson, J., Copenhagen, D. R., Storm-Mathisen, J., Chaudhry, F. A., Nicoll, R. A., & Edwards, R. H. (2004). Vesicular Glutamate Transporters 1 and 2 Target to Functionally Distinct Synaptic Release Sites. Science, 304(5678), 1815â1819.

Authors 9

Robert T. Fremeau (first)
Kaiwen Kam (additional)
Tayyaba Qureshi (additional)
Juliette Johnson (additional)
David R. Copenhagen (additional)
Jon Storm-Mathisen (additional)
Farrukh A. Chaudhry (additional)
Roger A. Nicoll (additional)
Robert H. Edwards (additional)

References 31 Referenced 419

10.1016/S0021-9258(19)37605-7
10.1016/S0021-9258(18)83243-4
10.1523/JNEUROSCI.19-01-00159.1999
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10.1038/35025070
10.1016/S0896-6273(01)00344-0
10.1523/JNEUROSCI.21-22-j0002.2001
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If both isoforms were present on the same vesicle the loss of VGLUT1 should have reduced quantal size assuming that the amount of transporter expressed limits the rate of vesicle filling. If however a single VGLUT protein suffices to fill a vesicle to thermodynamic equilibrium and if many vesicles contain VGLUT2 as well as VGLUT1 the knockout could not have substantially reduced excitatory transmission. A large number of synaptic vesicles must therefore contain only one isoform.
10.1038/366569a0
10.1126/science.7901909
10.1093/embo-reports/kvf159
10.1016/S0896-6273(02)00568-8
The ratio of vesicles >100 nm from the cell membrane/vesicles. <100 nm from the membrane was 1.73 ± 0.21 (mean ± SEM) in the wild type and 0.88 ± 0.14 in the knockout based on all the data. P = 0.004 by analysis of variance (General Linear Model MINITAB).
10.1038/375488a0
10.1083/jcb.134.5.1219
10.1111/j.1469-7793.2000.t01-1-00195.x
10.1152/jn.1999.81.6.2696
10.1126/science.287.5454.864
10.1038/22768
10.1016/S0896-6273(03)00088-6
Although the altered morphology of excitatory terminals might be thought to contribute to the enhanced short-term depression observed in VGLUT1 knockout mice the changes presumably occur at silent synapses that would otherwise have expressed VGLUT1 rather than the functional synapses expressing VGLUT2.
10.1046/j.1460-9568.2003.02698.x
We thank N. Killeen N. Calakos D. House V. Stein C. Zhou and G. Li for assistance and M. Scanziani H. Li and members of the Edwards Nicoll and Pleasure laboratories for suggestions. T.Q. F.A.C. and J.S.-M. were supported by the Norwegian Research Council and the European Union. K.K. is supported by NSF J.J. and D.R.C. by NIH R.T.F. by NINDS and R.H.E. by the National Institute of Mental Health National Institute on Drug Abuse National Institute of Neurological Disorders and Stroke and the Mathers Foundation. R.A.N. is a member of the Keck Center for Integrative Neuroscience and the Silvio Conte Center for Neuroscience Research and is supported by the NIH and the Bristol-Myers Squibb Co.

Dates

Type	When
Created	21 years, 4 months ago (May 3, 2004, 8:48 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 11:19 p.m.)
Indexed	3 days ago (Sept. 3, 2025, 6:47 a.m.)
Issued	21 years, 2 months ago (June 18, 2004)
Published	21 years, 2 months ago (June 18, 2004)
Published Print	21 years, 2 months ago (June 18, 2004)

Funders 0

None

BibTeX

@article{Fremeau_2004, title={Vesicular Glutamate Transporters 1 and 2 Target to Functionally Distinct Synaptic Release Sites}, volume={304}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1097468}, DOI={10.1126/science.1097468}, number={5678}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Fremeau, Robert T. and Kam, Kaiwen and Qureshi, Tayyaba and Johnson, Juliette and Copenhagen, David R. and Storm-Mathisen, Jon and Chaudhry, Farrukh A. and Nicoll, Roger A. and Edwards, Robert H.}, year={2004}, month=jun, pages={1815–1819} }

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