The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate

  1. Robert T. Fremeau, Jr.*,,
  2. Jonathon Burman*,,
  3. Tayyaba Qureshi,
  4. Cindy H. Tran*,
  5. John Proctor*,
  6. Juliette Johnson§,
  7. Hui Zhang,
  8. David Sulzer,
  9. David R. Copenhagen§,
  10. Jon Storm-Mathisen,
  11. Richard J. Reimer*,,
  12. Farrukh A. Chaudhry, and
  13. Robert H. Edwards*,**
  1. Departments of *Neurology and Physiology and§ Ophthalmology and Physiology, Graduate Programs in Neuroscience and Cell Biology, University of California School of Medicine, San Francisco, CA 94143; Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, N-0317 Oslo, Norway; and Departments of Neurology and Psychiatry, Columbia University, Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032
  1. Communicated by Roger A. Nicoll, University of California, San Francisco, CA (received for review July 30, 2002)

Abstract

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.

Footnotes

  • 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{at}itsa.ucsf.edu.

  • Abbreviations:
    1. VGLUT, vesicular glutamate transporter

    2. GAD, glutamic acid decarboxylase

    3. GABA, γ-aminobutyric acid

    4. ACh, acetylcholine

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