Microtubules restrict F-actin polymerization to the immune synapse via GEF-H1 to maintain polarity in lymphocytes
- Institute Curie, France
- 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
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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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
Further reading
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- Cell Biology
Cytoskeleton rearrangements promote formation of a giant structure called a GUVac that stops cells from dying when they become detached from the extracellular matrix.
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