Journal
EMBO JOURNAL
Volume 28, Issue 10, Pages 1518-1530Publisher
WILEY
DOI: 10.1038/emboj.2009.86
Keywords
analytical ultracentrifugation; crystallography; desensitization; glutamate receptors; synaptic transmission
Categories
Funding
- NICHD
- NIH
- DHHS
- NIBIB
- Helen Hay Whitney Foundation
- [RO1 NS 050655]
Ask authors/readers for more resources
AMPA and kainate receptors mediate fast synaptic transmission. AMPA receptor ligand-binding domains form dimers, which are key functional units controlling ion-channel activation and desensitization. Dimer stability is inversely related to the rate and extent of desensitization. Kainate and AMPA receptors share common structural elements, but functional measurements suggest that subunit assembly and gating differs between these subtypes. To investigate this, we constructed a library of GluR6 kainate receptor mutants and directly measured changes in kainate receptor dimer stability by analytical ultracentrifugation, which, combined with electrophysiological experiments, revealed an inverse correlation between dimer stability and the rate of desensitization. We solved crystal structures for a series of five GluR6 mutants, to understand the molecular mechanisms for dimer stabilization. We demonstrate that the desensitized state of kainate receptors acts as a deep energy well offsetting the stabilizing effects of dimer interface mutants, and that the deactivation of kainate receptor responses is dominated by entry into desensitized states. Our results show how neurotransmitter receptors with similar structures and gating mechanisms can exhibit strikingly different functional properties. The EMBO Journal (2009) 28, 1518-1530. doi:10.1038/emboj.2009.86; Published online 2 April 2009
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available