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Science 304 (5678): 1815-1819

Copyright © 2004 by the American Association for the Advancement of Science

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

Robert T. Fremeau, Jr.,1,2* Kaiwen Kam,2,3* Tayyaba Qureshi,5 Juliette Johnson,2,4 David R. Copenhagen,2,4 Jon Storm-Mathisen,5 Farrukh A. Chaudhry,5 Roger A. Nicoll,2,3{dagger} Robert H. Edwards1,2{dagger}

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.

1 Department of Neurology, Graduate Programs in Neuroscience and Cell Biology, University of California San Francisco School of Medicine, CA 94143, USA.
2 Department of Physiology, Graduate Programs in Neuroscience and Cell Biology, University of California San Francisco School of Medicine, CA 94143, USA.
3 Department of Cellular and Molecular Pharmacology, Graduate Programs in Neuroscience and Cell Biology, University of California San Francisco School of Medicine, CA 94143, USA.
4 Department of Ophthalmology, Graduate Programs in Neuroscience and Cell Biology, University of California San Francisco School of Medicine, CA 94143, USA.
5 Anatomical Institute and Centre for Molecular Biology and Neuroscience, University of Oslo, Post Office Box 1105 Blindern, N-0317 Oslo, Norway.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: edwards{at}itsa.ucsf.edu (R.H.E.); nicoll{at}cmp.ucsf.edu (R.A.N.)

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