SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling
- University of New South Wales, Australia
- University of Konstanz, Switzerland
- The University of New South Wales, Australia
Abstract
T cell activation requires engagement of a cognate antigen by the T cell receptor (TCR) and the co-stimulatory signal of CD28. Both TCR and CD28 aggregate into clusters at the plasma membrane of activated T cells. While the role of TCR clustering in T cell activation has been extensively investigated, little is known about how CD28 clustering contributes to CD28 signalling. Here we report that upon CD28 triggering, the BAR-domain protein sorting nexin 9 (SNX9) is recruited to CD28 clusters at the immunological synapse. Using three-dimensional correlative light and electron microscopy, we show that SNX9 generates membrane tubulation out of CD28 clusters. Our data further reveal that CD28 clusters are in fact dynamic structures and that SNX9 regulates their stability as well as CD28 phosphorylation and the resulting production of the cytokine IL-2. In summary, our work suggests a model in which SNX9-mediated tubulation generates a membrane environment that promotes CD28 triggering and downstream signalling events.
Data availability
All datasets for this study are deposited on Zenodo and are publicly available under a Creative Commons Attribution 4.0 International license
Article and author information
Author details
Funding
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_172969)
- Jérémie Rossy
Deutsche Forschungsgemeinschaft (RO 6238/1-1)
- Jérémie Rossy
National Health and Medical Research Council (APP1102730)
- Jérémie Rossy
Novartis Stiftung für Medizinisch-Biologische Forschung
- Jérémie Rossy
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bernard Malissen, Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, France
Version history
- Received: February 15, 2021
- Accepted: January 12, 2022
- Accepted Manuscript published: January 20, 2022 (version 1)
- Version of Record published: January 21, 2022 (version 2)
Copyright
© 2022, Ecker 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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SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling
eLife 11:e67550.
https://doi.org/10.7554/eLife.67550
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