Glutamate-binding affinity of Drosophila metabotropic glutamate receptor is modulated by association with lipid rafts.

Published

Journal Article

Metabotropic glutamate receptors (mGluRs) are responsible for the effects of glutamate in slow synaptic transmission, and are implicated in the regulation of many processes in the CNS. Recently, we have reported the expression and purification of a mGluR from Drosophila melanogaster (DmGluRA), a homologue of mammalian group II mGluRs. We have shown that ligand binding to reconstituted DmGluRA requires the presence of ergosterol in the liposomes [Eroglu, C., Cronet, P., Panneels, V., Beaufils, P. & Sinning, I. (2002) EMBO Rep. 3, 491-496]. Here we demonstrate that the receptor exists in different affinity states for glutamate, depending on the membrane composition. The receptor is in a high-affinity state when associated with sterol-rich lipid microdomains (rafts), and in a low-affinity state out of rafts. Enrichment of the membranes with cholesterol shifts the receptor into the high-affinity state, and induces its association with rafts. The receptor was crosslinked to photocholesterol. Our data suggest that sterol-rich lipid rafts act as positive allosteric regulators of DmGluRA.

Full Text

Duke Authors

Cited Authors

  • Eroglu, C; Brugger, B; Wieland, F; Sinning, I

Published Date

  • September 2, 2003

Published In

Volume / Issue

  • 100 / 18

Start / End Page

  • 10219 - 10224

PubMed ID

  • 12923296

Pubmed Central ID

  • 12923296

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1737042100

Language

  • eng

Conference Location

  • United States