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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,5Juliette Johnson,2,4David R. Copenhagen,2,4Jon Storm-Mathisen,5Farrukh A. Chaudhry,5Roger A. Nicoll,2,3Robert H. Edwards1,2
Vesicular glutamate transporters (VGLUTs) 1 and 2 show a mutuallyexclusive distribution in the adult brain that suggests specializationfor synapses with different properties of release. Consistentwith this distribution, inactivation of the VGLUT1 gene silenceda subset ofexcitatory neurons in the adult. However, the samecell populations exhibited VGLUT1-independent transmission earlyin life. Developing hippocampal neurons transiently coexpressedVGLUT2 and VGLUT1 at distinct synaptic sites with differentshort-term plasticity. The loss of VGLUT1 also reduced the reservepool of synaptic vesicles. Thus, VGLUT1 plays an unanticipatedrole 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.
* These authors contributed equally to this work.
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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