SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling
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 investigate...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-01-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/67550 |
| _version_ | 1811236763087142912 |
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| author | Manuela Ecker Richard Schregle Natasha Kapoor-Kaushik Pascal Rossatti Verena M Betzler Daryan Kempe Maté Biro Nicholas Ariotti Gregory MI Redpath Jeremie Rossy |
| author_facet | Manuela Ecker Richard Schregle Natasha Kapoor-Kaushik Pascal Rossatti Verena M Betzler Daryan Kempe Maté Biro Nicholas Ariotti Gregory MI Redpath Jeremie Rossy |
| author_sort | Manuela Ecker |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T12:13:48Z |
| format | Article |
| id | doaj.art-9fa3ef129084483c9e4e569334eb2288 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:13:48Z |
| publishDate | 2022-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-9fa3ef129084483c9e4e569334eb22882022-12-22T03:33:30ZengeLife Sciences Publications LtdeLife2050-084X2022-01-011110.7554/eLife.67550SNX9-induced membrane tubulation regulates CD28 cluster stability and signallingManuela Ecker0Richard Schregle1Natasha Kapoor-Kaushik2Pascal Rossatti3Verena M Betzler4Daryan Kempe5Maté Biro6https://orcid.org/0000-0001-5852-3726Nicholas Ariotti7Gregory MI Redpath8Jeremie Rossy9https://orcid.org/0000-0002-5128-5283EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, AustraliaBiotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland; Department of Biology, University of Konstanz, Konstanz, GermanyElectron Microscopy Unit, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, AustraliaBiotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, SwitzerlandBiotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, SwitzerlandEMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, AustraliaEMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, AustraliaElectron Microscopy Unit, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia; Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, AustraliaEMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, AustraliaEMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, Australia; Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland; Department of Biology, University of Konstanz, Konstanz, GermanyT 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.https://elifesciences.org/articles/67550T cellsCD28membrane curvaturemembrane organisationsignallingsorting nexin 9 |
| spellingShingle | Manuela Ecker Richard Schregle Natasha Kapoor-Kaushik Pascal Rossatti Verena M Betzler Daryan Kempe Maté Biro Nicholas Ariotti Gregory MI Redpath Jeremie Rossy SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling eLife T cells CD28 membrane curvature membrane organisation signalling sorting nexin 9 |
| title | SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling |
| title_full | SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling |
| title_fullStr | SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling |
| title_full_unstemmed | SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling |
| title_short | SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling |
| title_sort | snx9 induced membrane tubulation regulates cd28 cluster stability and signalling |
| topic | T cells CD28 membrane curvature membrane organisation signalling sorting nexin 9 |
| url | https://elifesciences.org/articles/67550 |
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