1. Neuroscience

SUMOylation of NaV1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons

  1. Oron Kotler
  2. Yana Khrapunsky
  3. Arik Shvartsman
  4. Hui Dai
  5. Leigh D Plant
  6. Steven AN Goldstein  Is a corresponding author
  7. Ilya Fleidervish  Is a corresponding author
  1. Ben-Gurion University of the Negev, Israel
  2. University of California, Irvine, United States
  3. Northeastern University, United States
https://doi.org/10.7554/eLife.81463
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  1. Oron Kotler
  2. Yana Khrapunsky
  3. Arik Shvartsman
  4. Hui Dai
  5. Leigh D Plant
  6. Steven AN Goldstein
  7. Ilya Fleidervish
(2023)
SUMOylation of NaV1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons
eLife 12:e81463.
https://doi.org/10.7554/eLife.81463
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Abstract

Voltage-gated sodium channels located in axon initial segments (AIS) trigger action potentials (AP) and play pivotal roles in the excitability of cortical pyramidal neurons. The differential electrophysiological properties and distributions of NaV1.2 and NaV1.6 channels lead to distinct contributions to AP initiation and propagation. While NaV1.6 at the distal AIS promotes AP initiation and forward propagation, NaV1.2 at the proximal AIS promotes the backpropagation of APs to the soma. Here, we show the Small Ubiquitin-like Modifier (SUMO) pathway modulates Na+ channels at the AIS to increase neuronal gain and the speed of backpropagation. Since SUMO does not affect NaV1.6, these effects were attributed to SUMOylation of NaV1.2. Moreover, SUMO effects were absent in a mouse engineered to express NaV1.2-Lys38Gln channels that lack the site for SUMO linkage. Thus, SUMOylation of NaV1.2 exclusively controls INaP generation and AP backpropagation, thereby playing a prominent role in synaptic integration and plasticity.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting file; the Source Data files will be uploaded to the Dryad server promptly

The following data sets were generated

Article and author information

Author details

  1. Oron Kotler

    Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    The authors declare that no competing interests exist.

  2. Yana Khrapunsky

    Depatrment of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    The authors declare that no competing interests exist.

  3. Arik Shvartsman

    Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer Sheva, Israel
    Competing interests
    The authors declare that no competing interests exist.

  4. Hui Dai

    Department of Pediatrics, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Leigh D Plant

    Department of Pharmaceutical Sciences, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1622-1655

  6. Steven AN Goldstein

    Department of Pediatrics, University of California, Irvine, Irvine, United States
    For correspondence
    sgoldst2@hs.uci.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5207-5061

  7. Ilya Fleidervish

    Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Beer Sheva, Israel
    For correspondence
    ilya@bgu.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5501-726X

Funding

Israel Science Foundation (1384/19)

  • Ilya Fleidervish

National Institutes of Health (R01HL10549)

  • Steven AN Goldstein

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

Reviewing Editor

  1. Teresa Giraldez, University of La Laguna, Spain

Ethics

Animal experimentation: This study was carried out at the Ben-Gurion University of the Negev in accordance with the recommendations of guidelines for the welfare of experimental animals. Animal experiments were approved by the Institutional Animal Care and Use Committee of Ben-Gurion University (protocols IL-68-09-2019(A), IL-79-10-2020(D)).

Version history

  1. Received: June 28, 2022
  2. Preprint posted: August 3, 2022 (view preprint)
  3. Accepted: February 15, 2023
  4. Accepted Manuscript published: February 16, 2023 (version 1)
  5. Version of Record published: March 14, 2023 (version 2)

Copyright

© 2023, Kotler 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. Oron Kotler
  2. Yana Khrapunsky
  3. Arik Shvartsman
  4. Hui Dai
  5. Leigh D Plant
  6. Steven AN Goldstein
  7. Ilya Fleidervish
(2023)
SUMOylation of NaV1.2 channels regulates the velocity of backpropagating action potentials in cortical pyramidal neurons
eLife 12:e81463.
https://doi.org/10.7554/eLife.81463

Share this article

https://doi.org/10.7554/eLife.81463

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