SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling

Abstract
Data availability
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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

The following data sets were generated

1. Manuela Ecker; Nicholas Ariotti; Gregory M. Redpath; Jeremie Rossy
(2022) SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling
10.5281/zenodo.5838426.

https://zenodo.org/record/5838426#.YegMjC9r3Mg

Article and author information

Author details

Ecker Ecker

EMBL Australia Node in Single Molecule Science, University of New South Wales, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Richard Schregle

Biotechnology Institute Thurgau, University of Konstanz, Kreuzlingen, Switzerland

Competing interests
The authors declare that no competing interests exist.
Natasha Kapoor-Kaushik

Electron Microscope Unit, University of New South Wales, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Pascal Rossatti

Biotechnology Institute Thurgau, University of Konstanz, Kreuzlingen, Switzerland

Competing interests
The authors declare that no competing interests exist.
Verena M Betzler

Biotechnology Institute Thurgau, University of Konstanz, Kreuzlingen, Switzerland

Competing interests
The authors declare that no competing interests exist.
Daryan Kempe

EMBL Australia Node in Single Molecule Science, University of New South Wales, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Maté Biro

EMBL Australia Node in Single Molecule Science, University of New South Wales, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5852-3726
Nicholas Ariotti

Electron Microscope Unit, University of New South Wales, Sydney, Australia

Competing interests
The authors declare that no competing interests exist.
Gregory MI Redpath

EMBL Australia Node in Single Molecule Science, The University of New South Wales, Sydney, Australia

For correspondence
gregmi.redpath@gmail.com

Competing interests
The authors declare that no competing interests exist.
Jérémie Rossy

Biotechnology Institute Thurgau, University of Konstanz, Kreuzlingen, Switzerland

For correspondence
jeremie.rossy@bitg.ch

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5128-5283

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.

Copyright

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.