The Identification of Vesicular Glutamate Transporter 3 Suggests Novel Modes of Signaling by Glutamate

Quantal release of the principal excitatory neurotransmitter glutamate requires a mechanism for its transport into secretory vesicles. Within the brain, the complementary expression of vesicular glutamate transporters (VGLUTs) 1 and 2 accounts for the release of glutamate by all known excitatory neu...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 99; no. 22; pp. 14488 - 14493
Main Authors Fremeau, Robert T., Burman, Jonathon, Qureshi, Tayyaba, Tran, Cindy H., Proctor, John, Johnson, Juliette, Zhang, Hui, Sulzer, David, Copenhagen, David R., Storm-Mathisen, Jon, Reimer, Richard J., Chaudhry, Farrukh A., Edwards, Robert H.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 29.10.2002
National Acad Sciences
Subjects
Amacrine cells
Amino Acid Transport Systems, Acidic - genetics
Amino Acid Transport Systems, Acidic - metabolism
Animals
Biological Sciences
Blood vessels
Brain - metabolism
Brain - pathology
Cell Membrane - metabolism
Cell nucleus
Dendrites
Dendrites - metabolism
Glutamic Acid - metabolism
Hippocampus
Humans
Hydrogen-Ion Concentration
Kidney - metabolism
Kidney - pathology
Liver - metabolism
Liver - pathology
Male
Neuroglia
Neurology
Neurons
PC12 Cells
Purkinje cells
Pyramidal cells
Rats
Signal Transduction
Synapses
Tissue Distribution
Vesicular Glutamate Transport Proteins
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Summary:Quantal release of the principal excitatory neurotransmitter glutamate requires a mechanism for its transport into secretory vesicles. Within the brain, the complementary expression of vesicular glutamate transporters (VGLUTs) 1 and 2 accounts for the release of glutamate by all known excitatory neurons. We now report the identification of VGLUT3 and its expression by many cells generally considered to release a classical transmitter with properties very different from glutamate. Remarkably, subpopulations of inhibitory neurons as well as cholinergic interneurons, monoamine neurons, and glia express VGLUT3. The dendritic expression of VGLUT3 by particular neurons also indicates the potential for retrograde synaptic signaling. The distribution and subcellular location of VGLUT3 thus suggest novel modes of signaling by glutamate.
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R.T.F. and J.B. contributed equally to this work.
Present address: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, P211 MSLS, 1201 Welch Road, Stanford, CA 94305.
To whom correspondence should be addressed. E-mail: edwards@itsa.ucsf.edu.
Communicated by Roger A. Nicoll, University of California, San Francisco, CA
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.222546799