Microtubule plus-end dynamics link wound repair to the innate immune response

  1. Clara Taffoni
  2. Shizue Omi
  3. Caroline Huber
  4. Sébastien Mailfert
  5. Matthieu Fallet
  6. Jean-François Rupprecht
  7. Jonathan Ewbank
  8. Nathalie Pujol  Is a corresponding author
  1. Aix Marseille Université, INSERM, CNRS, France
  2. Aix Marseille Université, CNRS UMR7332, France

Abstract

The skin protects animals from infection and physical damage. In C. elegans, wounding the epidermis triggers an immune reaction and a repair response, but it is not clear how these are coordinated. Previous work implicated the microtubule cytoskeleton in the maintenance of epidermal integrity (Chuang et al, 2016). Here, by establishing a simple wounding system, we show that wounding provokes a reorganisation of plasma membrane subdomains. This is followed by recruitment of the microtubule plus end-binding protein EB1/EBP-2 around the wound and actin ring formation, dependant on ARP2/3 branched actin polymerisation. We show that microtubule dynamics are required for the recruitment and closure of the actin ring, and for the trafficking of the key signalling protein SLC6/SNF-12 towards the injury site. Without SNF-12 recruitment, there is an abrogation of the immune response. Our results suggest that microtubule dynamics coordinate the cytoskeletal changes required for wound repair and the concomitant activation of innate immunity.

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 quantitative Figures.

Article and author information

Author details

  1. Clara Taffoni

    CIML, Centre d'Immunologie de Marseille-Luminy, Turing Centre for Living Systems, Aix Marseille Université, INSERM, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9265-5909
  2. Shizue Omi

    CIML, Centre d'Immunologie de Marseille-Luminy, Turing Centre for Living Systems, Aix Marseille Université, INSERM, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2711-2016
  3. Caroline Huber

    CIML, Centre d'Immunologie de Marseille-Luminy, Turing Centre for Living Systems, Aix Marseille Université, INSERM, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3767-2719
  4. Sébastien Mailfert

    CIML, Centre d'Immunologie de Marseille-Luminy, Turing Centre for Living Systems, Aix Marseille Université, INSERM, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0409-0432
  5. Matthieu Fallet

    CIML, Centre d'Immunologie de Marseille-Luminy, Turing Centre for Living Systems, Aix Marseille Université, INSERM, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8144-6159
  6. Jean-François Rupprecht

    CPT, Turing Centre for Living Systems, Aix Marseille Université, CNRS UMR7332, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8904-5878
  7. Jonathan Ewbank

    CIML, Centre d'Immunologie de Marseille-Luminy, Turing Centre for Living Systems, Aix Marseille Université, INSERM, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1257-6862
  8. Nathalie Pujol

    CIML, Centre d'Immunologie de Marseille-Luminy, Turing Centre for Living Systems, Aix Marseille Université, INSERM, CNRS, Marseille, France
    For correspondence
    pujol@ciml.univ-mrs.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8889-3197

Funding

Agence Nationale de la Recherche (ANR-16-CE15-0001-01)

  • Clara Taffoni
  • Sébastien Mailfert
  • Matthieu Fallet
  • Jonathan Ewbank
  • Nathalie Pujol

Institut National de la Santé et de la Recherche Médicale

  • Jonathan Ewbank

Centre National de la Recherche Scientifique

  • Shizue Omi
  • Sébastien Mailfert
  • Matthieu Fallet
  • Jean-François Rupprecht
  • Nathalie Pujol

Aix-Marseille Université

  • Clara Taffoni
  • Caroline Huber

Agence Nationale de la Recherche (ANR-12-BSV3-0001-01)

  • Clara Taffoni
  • Sébastien Mailfert
  • Matthieu Fallet
  • Jonathan Ewbank
  • Nathalie Pujol

Agence Nationale de la Recherche (ANR-11-LABX-0054)

  • Clara Taffoni
  • Sébastien Mailfert
  • Matthieu Fallet
  • Jonathan Ewbank
  • Nathalie Pujol

Agence Nationale de la Recherche (ANR-11-IDEX-0001-02)

  • Clara Taffoni
  • Sébastien Mailfert
  • Matthieu Fallet
  • Jonathan Ewbank
  • Nathalie Pujol

Agence Nationale de la Recherche (ANR-10-INBS-04-01)

  • Clara Taffoni
  • Sébastien Mailfert
  • Matthieu Fallet
  • Jonathan Ewbank
  • Nathalie Pujol

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

Reviewing Editor

  1. Terry Lechler, Duke University, United States

Version history

  1. Received: January 11, 2019
  2. Accepted: January 27, 2020
  3. Accepted Manuscript published: January 29, 2020 (version 1)
  4. Version of Record published: February 26, 2020 (version 2)

Copyright

© 2020, Taffoni 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

  • 2,787
    views
  • 426
    downloads
  • 25
    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. Clara Taffoni
  2. Shizue Omi
  3. Caroline Huber
  4. Sébastien Mailfert
  5. Matthieu Fallet
  6. Jean-François Rupprecht
  7. Jonathan Ewbank
  8. Nathalie Pujol
(2020)
Microtubule plus-end dynamics link wound repair to the innate immune response
eLife 9:e45047.
https://doi.org/10.7554/eLife.45047

Share this article

https://doi.org/10.7554/eLife.45047

Further reading

    1. Cell Biology
    Tengteng Huang, Xiaoling Chen ... Zhiqing Huang
    Research Article

    Metabolic disorders are highly prevalent in modern society. Exercise mimetics are defined as pharmacological compounds that can produce the beneficial effects of fitness. Recently, there has been increased interest in the role of eugenol and transient receptor potential vanilloid 1 (TRPV1) in improving metabolic health. The aim of this study was to investigate whether eugenol acts as an exercise mimetic by activating TRPV1. Here, we showed that eugenol improved endurance capacity, caused the conversion of fast-to-slow muscle fibers, and promoted white fat browning and lipolysis in mice. Mechanistically, eugenol promoted muscle fiber-type transformation by activating TRPV1-mediated CaN signaling pathway. Subsequently, we identified IL-15 as a myokine that is regulated by the CaN/nuclear factor of activated T cells cytoplasmic 1 (NFATc1) signaling pathway. Moreover, we found that TRPV1-mediated CaN/NFATc1 signaling, activated by eugenol, controlled IL-15 levels in C2C12 myotubes. Our results suggest that eugenol may act as an exercise mimetic to improve metabolic health via activating the TRPV1-mediated CaN signaling pathway.

    1. Cell Biology
    Yi-Ju Chen, Shun-Cheng Tseng ... Eric Hwang
    Research Article

    A functional nervous system is built upon the proper morphogenesis of neurons to establish the intricate connection between them. The microtubule cytoskeleton is known to play various essential roles in this morphogenetic process. While many microtubule-associated proteins (MAPs) have been demonstrated to participate in neuronal morphogenesis, the function of many more remains to be determined. This study focuses on a MAP called HMMR in mice, which was originally identified as a hyaluronan binding protein and later found to possess microtubule and centrosome binding capacity. HMMR exhibits high abundance on neuronal microtubules and altering the level of HMMR significantly affects the morphology of neurons. Instead of confining to the centrosome(s) like cells in mitosis, HMMR localizes to microtubules along axons and dendrites. Furthermore, transiently expressing HMMR enhances the stability of neuronal microtubules and increases the formation frequency of growing microtubules along the neurites. HMMR regulates the microtubule localization of a non-centrosomal microtubule nucleator TPX2 along the neurite, offering an explanation for how HMMR contributes to the promotion of growing microtubules. This study sheds light on how cells utilize proteins involved in mitosis for non-mitotic functions.