1. Neuroscience

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
https://doi.org/10.7554/eLife.09693
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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.

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

  • 2,546
    views
  • 631
    downloads
  • 55
    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

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Synaptic deregulation of cholinergic projection neurons causes olfactory dysfunction across five fly Parkinsonism models

    Ulrike Pech, Jasper Janssens ... Patrik Verstreken
    Research Article

    The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence of nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to the emergence of motor issues, patients frequently experience non-motor symptoms, such as a reduced sense of smell (hyposmia). The cellular and molecular bases for these early defects remain enigmatic. To explore this, we developed a new collection of five fruit fly models of familial Parkinsonism and conducted single-cell RNA sequencing on young brains of these models. Interestingly, cholinergic projection neurons are the most vulnerable cells, and genes associated with presynaptic function are the most deregulated. Additional single nucleus sequencing of three specific brain regions of Parkinson’s disease patients confirms these findings. Indeed, the disturbances lead to early synaptic dysfunction, notably affecting cholinergic olfactory projection neurons crucial for olfactory function in flies. Correcting these defects specifically in olfactory cholinergic interneurons in flies or inducing cholinergic signaling in Parkinson mutant human induced dopaminergic neurons in vitro using nicotine, both rescue age-dependent dopaminergic neuron decline. Hence, our research uncovers that one of the earliest indicators of disease in five different models of familial Parkinsonism is synaptic dysfunction in higher-order cholinergic projection neurons and this contributes to the development of hyposmia. Furthermore, the shared pathways of synaptic failure in these cholinergic neurons ultimately contribute to dopaminergic dysfunction later in life.

    1. Neuroscience

    Serotonin modulates infraslow oscillation in the dentate gyrus during non-REM sleep

    Gergely F Turi, Sasa Teng ... Yueqing Peng
    Research Article

    Synchronous neuronal activity is organized into neuronal oscillations with various frequency and time domains across different brain areas and brain states. For example, hippocampal theta, gamma, and sharp wave oscillations are critical for memory formation and communication between hippocampal subareas and the cortex. In this study, we investigated the neuronal activity of the dentate gyrus (DG) with optical imaging tools during sleep-wake cycles in mice. We found that the activity of major glutamatergic cell populations in the DG is organized into infraslow oscillations (0.01–0.03 Hz) during NREM sleep. Although the DG is considered a sparsely active network during wakefulness, we found that 50% of granule cells and about 25% of mossy cells exhibit increased activity during NREM sleep, compared to that during wakefulness. Further experiments revealed that the infraslow oscillation in the DG was correlated with rhythmic serotonin release during sleep, which oscillates at the same frequency but in an opposite phase. Genetic manipulation of 5-HT receptors revealed that this neuromodulatory regulation is mediated by Htr1a receptors and the knockdown of these receptors leads to memory impairment. Together, our results provide novel mechanistic insights into how the 5-HT system can influence hippocampal activity patterns during sleep.