Preferential assembly of heteromeric kainate and AMPA receptor amino terminal domains

  1. Huaying Zhao  Is a corresponding author
  2. Suvendu Lomash
  3. Sagar Chittori
  4. Carla Glasser
  5. Mark L Mayer  Is a corresponding author
  6. Peter Schuck  Is a corresponding author
  1. National Institutes of Health, United States

Abstract

Ion conductivity and the gating characteristics of tetrameric glutamate receptor ion channels are determined by their subunit composition. Competitive homo- and hetero-dimerization of their amino-terminal domains (ATDs) is a key step controlling assembly. Here we measured systematically the thermodynamic stabilities of homodimers and heterodimers of kainate and AMPA receptors using fluorescence-detected sedimentation velocity analytical ultracentrifugation. Measured affinities span many orders of magnitude, and complexes show large differences in kinetic stabilities. The association of kainate receptor ATD dimers is generally weaker than the association of AMPA receptor ATD dimers, but both show a general pattern of increased heterodimer stability as compared to the homodimers of their constituents, matching well physiologically observed receptor combinations. The free energy maps of AMPA and kainate receptor ATD dimers provide a framework for the interpretation of observed receptor subtype combinations and possible assembly pathways.

Article and author information

Author details

  1. Huaying Zhao

    Dynamics of Molecular Assembly Section, Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States
    For correspondence
    zhaoh3@mail.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
  2. Suvendu Lomash

    Laboratory of Cellular and Molecular Neurophysiology, Porter Neuroscience Research Center, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sagar Chittori

    Laboratory of Cellular and Molecular Neurophysiology, Porter Neuroscience Research Center, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1417-6552
  4. Carla Glasser

    Laboratory of Cellular and Molecular Neurophysiology, Porter Neuroscience Research Center, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Mark L Mayer

    Laboratory of Cellular and Molecular Neurophysiology, Porter Neuroscience Research Center, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States
    For correspondence
    mark.mayer@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
  6. Peter Schuck

    Dynamics of Molecular Assembly Section, Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, United States
    For correspondence
    schuckp@mail.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8859-6966

Funding

National Institutes of Health (ZIA EB000008-11)

  • Peter Schuck

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Gary L Westbrook, Vollum Institute, United States

Publication history

  1. Received: September 15, 2017
  2. Accepted: October 22, 2017
  3. Accepted Manuscript published: October 23, 2017 (version 1)
  4. Accepted Manuscript updated: October 25, 2017 (version 2)
  5. Version of Record published: November 1, 2017 (version 3)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Huaying Zhao
  2. Suvendu Lomash
  3. Sagar Chittori
  4. Carla Glasser
  5. Mark L Mayer
  6. Peter Schuck
(2017)
Preferential assembly of heteromeric kainate and AMPA receptor amino terminal domains
eLife 6:e32056.
https://doi.org/10.7554/eLife.32056

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