Microtubules restrict F-actin polymerization to the immune synapse via GEF-H1 to maintain polarity in lymphocytes

  1. Judith Pineau
  2. Léa Pinon
  3. Olivier Mesdjian
  4. Jacques Fattaccioli
  5. Ana-Maria Lennon-Duménil  Is a corresponding author
  6. Paolo Pierobon  Is a corresponding author
  1. Institute Curie, France
  2. Ecole Normale Supérieure, France

Abstract

Immune synapse formation is a key step for lymphocyte activation. In B lymphocytes, the immune synapse controls the production of high-affinity antibodies, thereby defining the efficiency of humoral immune responses. While the key roles played by both the actin and microtubule cytoskeletons in the formation and function of the immune synapse have become increasingly clear, how the different events involved in synapse formation are coordinated in space and time by actin-microtubule interactions is not understood. Using a microfluidic pairing device, we studied with unprecedented resolution the dynamics of the various events leading to immune synapse formation and maintenance in murine B cells. Our results identify two groups of events, local and global dominated by actin and microtubules dynamics, respectively. They further highlight an unexpected role for microtubules and the GEF-H1-RhoA axis in restricting F-actin polymerization at the lymphocyte-antigen contact site, thereby allowing the formation and maintenance of a unique competent immune synapse.

Data availability

All data generated or analyzed during this study are included in the manuscript source data files and supporting files. Custom image analysis scripts are available online at https://github.com/PierobonLab/Paper-Pineau2022.

Article and author information

Author details

  1. Judith Pineau

    INSERM-U932- Immunité et Cancer, Institute Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0665-1210
  2. Léa Pinon

    Département de Chimie, Ecole Normale Supérieure, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Olivier Mesdjian

    Département de Chimie, Ecole Normale Supérieure, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Jacques Fattaccioli

    Département de Chimie, Ecole Normale Supérieure, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Ana-Maria Lennon-Duménil

    INSERM-U932- Immunité et Cancer, Institute Curie, Paris, France
    For correspondence
    Ana-Maria.Lennon@curie.fr
    Competing interests
    The authors declare that no competing interests exist.
  6. Paolo Pierobon

    INSERM-U932- Immunité et Cancer, Institute Curie, Paris, France
    For correspondence
    paolo.pierobon@curie.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3014-0181

Funding

Agence Nationale de la Recherche (ANR-15- CE18-0014-01)

  • Jacques Fattaccioli

Agence Nationale de la Recherche (ANR-21-CE30-0062-01 IMPerIS)

  • Judith Pineau
  • Paolo Pierobon

Agence Nationale de la Recherche (ANR-10-IDEX-0001-02 PSL*)

  • Judith Pineau
  • Ana-Maria Lennon-Duménil
  • Paolo Pierobon

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

Copyright

© 2022, Pineau 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. Judith Pineau
  2. Léa Pinon
  3. Olivier Mesdjian
  4. Jacques Fattaccioli
  5. Ana-Maria Lennon-Duménil
  6. Paolo Pierobon
(2022)
Microtubules restrict F-actin polymerization to the immune synapse via GEF-H1 to maintain polarity in lymphocytes
eLife 11:e78330.
https://doi.org/10.7554/eLife.78330

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https://doi.org/10.7554/eLife.78330

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