Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels

  1. Sharon Stevens
  2. Colleen M Longley
  3. Yuki Ogawa
  4. Lindsay Teliska
  5. Anithachristy Arumanayagam
  6. Supna Nair
  7. Juan A Oses-Prieto
  8. Alma L Burlingame
  9. Matthew Cykowski
  10. Mingshan Xue
  11. Matthew N Rasband  Is a corresponding author
  1. Baylor College of Medicine, United States
  2. Houston Methodist Hospital, United States
  3. University of California, San Francisco, United States

Abstract

Neuronal ankyrins cluster and link membrane proteins to the actin and spectrin-based cytoskeleton. Among the three vertebrate ankyrins, little is known about neuronal Ankyrin-R (AnkR). We report AnkR is highly enriched in Pv+ fast-spiking interneurons in mouse and human. We identify AnkR-associated protein complexes including cytoskeletal proteins, cell adhesion molecules (CAMs), and perineuronal nets (PNNs). We show that loss of AnkR from forebrain interneurons reduces and disrupts PNNs, decreases anxiety-like behaviors, and changes the intrinsic excitability and firing properties of Pv+ fast-spiking interneurons. These changes are accompanied by a dramatic reduction in Kv3.1b K+ channels. We identify a novel AnkR-binding motif in Kv3.1b, and show that AnkR is both necessary and sufficient for Kv3.1b membrane localization in interneurons and at nodes of Ranvier. Thus, AnkR regulates Pv+ fast-spiking interneuron function by organizing ion channels, CAMs, and PNNs, and linking these to the underlying b1 spectrin-based cytoskeleton.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all Figures.

Article and author information

Author details

  1. Sharon Stevens

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2238-8029
  2. Colleen M Longley

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8326-6143
  3. Yuki Ogawa

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Lindsay Teliska

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1733-6910
  5. Anithachristy Arumanayagam

    Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Supna Nair

    Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6499-0099
  7. Juan A Oses-Prieto

    Mass Spectrometry Facility, Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4759-2341
  8. Alma L Burlingame

    Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Matthew Cykowski

    Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Mingshan Xue

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1463-8884
  11. Matthew N Rasband

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    For correspondence
    rasband@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8184-2477

Funding

National Institute of Neurological Disorders and Stroke (NS044916)

  • Matthew N Rasband

National Institute of General Medical Sciences (GM103481)

  • Alma L Burlingame

National Institute of Mental Health (MH117089)

  • Mingshan Xue

National Institute of Neurological Disorders and Stroke (NS100893)

  • Mingshan Xue

National Institute of Neurological Disorders and Stroke (NS100300)

  • Sharon Stevens

National Institute of Mental Health (MH118804)

  • Colleen M Longley

National Institute of Neurological Disorders and Stroke (NS118584)

  • Matthew Cykowski

Dr. Miriam and Sheldon G. Adelson Medical Research Foundation

  • Alma L Burlingame
  • Matthew N Rasband

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

Ethics

Animal experimentation: All experiments were conducted in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Animal Care and Use Committee at Baylor College of Medicine under approval AN4634.

Reviewing Editor

  1. Dwight E Bergles, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: January 13, 2021
  2. Accepted: June 25, 2021
  3. Accepted Manuscript published: June 28, 2021 (version 1)
  4. Version of Record published: July 5, 2021 (version 2)

Copyright

© 2021, Stevens 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.

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  1. Sharon Stevens
  2. Colleen M Longley
  3. Yuki Ogawa
  4. Lindsay Teliska
  5. Anithachristy Arumanayagam
  6. Supna Nair
  7. Juan A Oses-Prieto
  8. Alma L Burlingame
  9. Matthew Cykowski
  10. Mingshan Xue
  11. Matthew N Rasband
(2021)
Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels
eLife 10:e66491.
https://doi.org/10.7554/eLife.66491

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