Block of Kainate Receptor Desensitization Uncovers a Key Trafficking Checkpoint

Avi Priel, Sanja Selak, Juan Lerma, Yael Stern-Bach*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

A prominent feature of ionotropic glutamate receptors from the AMPA and kainate subtypes is their profound desensitization in response to glutamate-a process thought to protect the neuron from overexcitation. In AMPA receptors, it is well established that desensitization results from rearrangements of the interface formed between agonist-binding domains of adjacent subunits; however, it is unclear how this mechanism applies to kainate receptors. Here we show that stabilization of the binding domain dimer by the generation of intermolecular disulfide bonds apparently blocked desensitization of the kainate receptor GluR6. This result establishes a common desensitization mechanism in both AMPA and kainate receptors. Surprisingly, however, surface expression of these nondesensitizing mutants was drastically reduced and did not depend on channel activity. Therefore, in addition to its role at the synapse, we now propose an intracellular role for desensitization in controlling maturation and trafficking of glutamate receptors.

Original languageAmerican English
Pages (from-to)1037-1046
Number of pages10
JournalNeuron
Volume52
Issue number6
DOIs
StatePublished - 21 Dec 2006

Bibliographical note

Funding Information:
This work was supported by grants to Y.S.-B. from the Israel Science Foundation (grant 561/03) and the European Commission (EUSynapse project; contract LSHM-CT-2005-019055) and to J.L. by the Spanish Ministry of Education and Science (grant BFU2006-07138). A.P. is a recipient of the David Kline prize of excellence by the Canadian Friends of the Hebrew University. S.S. is an I3P Program CSIC Research Fellow. We gratefully thank Rocio Rivera for her help with HEK293 cell transfections and Dr. Zehava Siegfried for her help with the manuscript.

Keywords

  • MOLNEURO
  • PROTEINS
  • SIGNALING

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