Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Nonvesicular release of glutamate by glial xCT transporters suppresses glutamate receptor clustering in vivo.

We hypothesized that cystine/glutamate transporters (xCTs) might be critical regulators of ambient extracellular glutamate levels in the nervous system and that misregulation of this glutamate pool might have important neurophysiological and/or behavioral consequences. To test this idea, we identified and functionally characterized a novel Drosophila xCT gene, which we subsequently named "genderblind" (gb). Genderblind is expressed in a previously overlooked subset of peripheral and central glia. Genetic elimination of gb causes a 50% reduction in extracellular glutamate concentration, demonstrating that xCT transporters are important regulators of extracellular glutamate. Consistent with previous studies showing that extracellular glutamate regulates postsynaptic glutamate receptor clustering, gb mutants show a large (200-300%) increase in the number of postsynaptic glutamate receptors. This increase in postsynaptic receptor abundance is not accompanied by other obvious synaptic changes and is completely rescued when synapses are cultured in wild-type levels of glutamate. Additional in situ pharmacology suggests that glutamate-mediated suppression of glutamate receptor clustering depends on receptor desensitization. Together, our results suggest that (1) xCT transporters are critical for regulation of ambient extracellular glutamate in vivo; (2) ambient extracellular glutamate maintains some receptors constitutively desensitized in vivo; and (3) constitutive desensitization of ionotropic glutamate receptors suppresses their ability to cluster at synapses.

Pubmed ID: 17202478 RIS Download

Mesh terms: Amino Acid Transport System y+ | Animals | Cells, Cultured | Drosophila | Drosophila Proteins | Neuroglia | Neurotransmitter Agents | Receptors, Glutamate | Synapses | Synaptic Transmission | Synaptic Vesicles | Tissue Distribution

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NINDS NIH HHS, Id: R01NS045628
  • Agency: NINDS NIH HHS, Id: R01 NS045628-04
  • Agency: NINDS NIH HHS, Id: R01 NS045628-01
  • Agency: NINDS NIH HHS, Id: R01 NS045628
  • Agency: NINDS NIH HHS, Id: R01 NS045628-02
  • Agency: NINDS NIH HHS, Id: R01 NS045628-03

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.