Auxiliary subunits of the CKAMP family differentially modulate AMPA receptor properties

  1. Paul Farrow
  2. Konstantin Khodosevich
  3. Yechiam Sapir
  4. Anton Schulmann
  5. Muhammad Aslam
  6. Yael Stern-Bach
  7. Hannah Monyer
  8. Jakob von Engelhardt  Is a corresponding author
  1. German Cancer Research Center, Germany
  2. Copenhagen University, Denmark
  3. Institute for Medical Research - Israel-Canada, Israel
  4. Heidelberg University, Germany

Abstract

AMPA receptor (AMPAR) function is modulated by auxiliary subunits. Here, we report on three AMPAR interacting proteins - namely CKAMP39, CKAMP52 and CKAMP59 - that, together with the previously characterized CKAMP44, constitute a novel family of auxiliary subunits distinct from other families of AMPAR interacting proteins. The new members of the CKAMP family display distinct regional and developmental expression profiles in the mouse brain. Notably, despite their structural similarities they exert diverse modulation on AMPAR gating by influencing deactivation, desensitization and recovery from desensitization, as well as glutamate and cyclothiazide potency to AMPARs. This study indicates that AMPAR function is very precisely controlled by the cell-type specific expression of the CKAMP family members.

Article and author information

Author details

  1. Paul Farrow

    Synaptic Signalling and Neurodegeneration, German Cancer Research Center, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Konstantin Khodosevich

    Biotech Research and Innovation Center, Copenhagen University, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  3. Yechiam Sapir

    Department of Biochemistry and Molecular Biology, Institute for Medical Research - Israel-Canada, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Anton Schulmann

    Department of Clinical Neurobiology, Medical Faculty, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Muhammad Aslam

    Synaptic Signalling and Neurodegeneration, German Cancer Research Center, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Yael Stern-Bach

    Department of Biochemistry and Molecular Biology, Institute for Medical Research - Israel-Canada, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  7. Hannah Monyer

    Department of Clinical Neurobiology, Medical Faculty, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Jakob von Engelhardt

    Synaptic Signalling and Neurodegeneration, German Cancer Research Center, Heidelberg, Germany
    For correspondence
    engelhardt@dzne.de
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Marlene Bartos, Albert-Ludwigs-Universität Freiburg, Germany

Version history

  1. Received: June 25, 2015
  2. Accepted: November 30, 2015
  3. Accepted Manuscript published: December 1, 2015 (version 1)
  4. Version of Record published: January 19, 2016 (version 2)
  5. Version of Record updated: October 11, 2018 (version 3)

Copyright

© 2015, Farrow et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,503
    views
  • 617
    downloads
  • 53
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Paul Farrow
  2. Konstantin Khodosevich
  3. Yechiam Sapir
  4. Anton Schulmann
  5. Muhammad Aslam
  6. Yael Stern-Bach
  7. Hannah Monyer
  8. Jakob von Engelhardt
(2015)
Auxiliary subunits of the CKAMP family differentially modulate AMPA receptor properties
eLife 4:e09693.
https://doi.org/10.7554/eLife.09693

Share this article

https://doi.org/10.7554/eLife.09693

Further reading

    1. Neuroscience
    James Malkin, Cian O'Donnell ... Laurence Aitchison
    Research Article

    Biological synaptic transmission is unreliable, and this unreliability likely degrades neural circuit performance. While there are biophysical mechanisms that can increase reliability, for instance by increasing vesicle release probability, these mechanisms cost energy. We examined four such mechanisms along with the associated scaling of the energetic costs. We then embedded these energetic costs for reliability in artificial neural networks (ANNs) with trainable stochastic synapses, and trained these networks on standard image classification tasks. The resulting networks revealed a tradeoff between circuit performance and the energetic cost of synaptic reliability. Additionally, the optimised networks exhibited two testable predictions consistent with pre-existing experimental data. Specifically, synapses with lower variability tended to have (1) higher input firing rates and (2) lower learning rates. Surprisingly, these predictions also arise when synapse statistics are inferred through Bayesian inference. Indeed, we were able to find a formal, theoretical link between the performance-reliability cost tradeoff and Bayesian inference. This connection suggests two incompatible possibilities: evolution may have chanced upon a scheme for implementing Bayesian inference by optimising energy efficiency, or alternatively, energy-efficient synapses may display signatures of Bayesian inference without actually using Bayes to reason about uncertainty.