SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling

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2022
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Ecker, Manuela
Kapoor-Kaushik, Natasha
Kempe, Daryan
Biro, Maté
Ariotti, Nicholas
Redpath, Gregory Mi
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eLife. eLife Sciences Publications. 2022, 11, e67550. eISSN 2050-084X. Available under: doi: 10.7554/eLife.67550
Zusammenfassung

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.

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570 Biowissenschaften, Biologie
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ISO 690ECKER, Manuela, Richard SCHREGLE, Natasha KAPOOR-KAUSHIK, Pascal ROSSATTI, Verena M. BETZLER, Daryan KEMPE, Maté BIRO, Nicholas ARIOTTI, Gregory Mi REDPATH, Jérémie ROSSY, 2022. SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling. In: eLife. eLife Sciences Publications. 2022, 11, e67550. eISSN 2050-084X. Available under: doi: 10.7554/eLife.67550
BibTex
@article{Ecker2022-01-20SNX9i-56518,
  year={2022},
  doi={10.7554/eLife.67550},
  title={SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling},
  volume={11},
  journal={eLife},
  author={Ecker, Manuela and Schregle, Richard and Kapoor-Kaushik, Natasha and Rossatti, Pascal and Betzler, Verena M. and Kempe, Daryan and Biro, Maté and Ariotti, Nicholas and Redpath, Gregory Mi and Rossy, Jérémie},
  note={Article Number: e67550}
}
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