Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway
The propagation and diversification of signals downstream of the T cell receptor (TCR) involve several adaptor proteins that control the assembly of multimolecular signaling complexes (signalosomes). The global characterization of changes in protein-protein interactions (PPI) following genetic pertu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1139123/full |
| _version_ | 1797870450110365696 |
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| author | Kilian Ruminski Javier Celis-Gutierrez Javier Celis-Gutierrez Nicolas Jarmuzynski Nicolas Jarmuzynski Emilie Maturin Stephane Audebert Marie Malissen Marie Malissen Luc Camoin Guillaume Voisinne Bernard Malissen Bernard Malissen Romain Roncagalli |
| author_facet | Kilian Ruminski Javier Celis-Gutierrez Javier Celis-Gutierrez Nicolas Jarmuzynski Nicolas Jarmuzynski Emilie Maturin Stephane Audebert Marie Malissen Marie Malissen Luc Camoin Guillaume Voisinne Bernard Malissen Bernard Malissen Romain Roncagalli |
| author_sort | Kilian Ruminski |
| collection | DOAJ |
| description | The propagation and diversification of signals downstream of the T cell receptor (TCR) involve several adaptor proteins that control the assembly of multimolecular signaling complexes (signalosomes). The global characterization of changes in protein-protein interactions (PPI) following genetic perturbations is critical to understand the resulting phenotypes. Here, by combining genome editing techniques in T cells and interactomics studies based on affinity purification coupled to mass spectrometry (AP-MS) analysis, we determined and quantified the molecular reorganization of the SLP76 interactome resulting from the ablation of each of the three GRB2-family adaptors. Our data showed that the absence of GADS or GRB2 induces a major remodeling of the PPI network associated with SLP76 following TCR engagement. Unexpectedly, this PPI network rewiring minimally affects proximal molecular events of the TCR signaling pathway. Nevertheless, during prolonged TCR stimulation, GRB2- and GADS-deficient cells displayed a reduced level of activation and cytokine secretion capacity. Using the canonical SLP76 signalosome, this analysis highlights the plasticity of PPI networks and their reorganization following specific genetic perturbations. |
| first_indexed | 2024-04-10T00:27:41Z |
| format | Article |
| id | doaj.art-5e912809456643aba8f129a48c1cf596 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T00:27:41Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5e912809456643aba8f129a48c1cf5962023-03-15T05:50:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.11391231139123Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathwayKilian Ruminski0Javier Celis-Gutierrez1Javier Celis-Gutierrez2Nicolas Jarmuzynski3Nicolas Jarmuzynski4Emilie Maturin5Stephane Audebert6Marie Malissen7Marie Malissen8Luc Camoin9Guillaume Voisinne10Bernard Malissen11Bernard Malissen12Romain Roncagalli13Centre d’Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, FranceCentre d’Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, FranceCentre d’Immunophénomique, Aix Marseille Université, INSERM, CNRS UMR, Marseille, FranceCentre d’Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, FranceCentre d’Immunophénomique, Aix Marseille Université, INSERM, CNRS UMR, Marseille, FranceCentre d’Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, FranceInstitut Paoli-Calmettes, CRCM, Aix Marseille Université, CNRS, INSERM, Marseille Protóomique, Marseille, FranceCentre d’Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, FranceCentre d’Immunophénomique, Aix Marseille Université, INSERM, CNRS UMR, Marseille, FranceInstitut Paoli-Calmettes, CRCM, Aix Marseille Université, CNRS, INSERM, Marseille Protóomique, Marseille, FranceCentre d’Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, FranceCentre d’Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, FranceCentre d’Immunophénomique, Aix Marseille Université, INSERM, CNRS UMR, Marseille, FranceCentre d’Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, FranceThe propagation and diversification of signals downstream of the T cell receptor (TCR) involve several adaptor proteins that control the assembly of multimolecular signaling complexes (signalosomes). The global characterization of changes in protein-protein interactions (PPI) following genetic perturbations is critical to understand the resulting phenotypes. Here, by combining genome editing techniques in T cells and interactomics studies based on affinity purification coupled to mass spectrometry (AP-MS) analysis, we determined and quantified the molecular reorganization of the SLP76 interactome resulting from the ablation of each of the three GRB2-family adaptors. Our data showed that the absence of GADS or GRB2 induces a major remodeling of the PPI network associated with SLP76 following TCR engagement. Unexpectedly, this PPI network rewiring minimally affects proximal molecular events of the TCR signaling pathway. Nevertheless, during prolonged TCR stimulation, GRB2- and GADS-deficient cells displayed a reduced level of activation and cytokine secretion capacity. Using the canonical SLP76 signalosome, this analysis highlights the plasticity of PPI networks and their reorganization following specific genetic perturbations.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1139123/fullTCRSLP76GRB2-family adaptorsmass spectrometryT cell signaling |
| spellingShingle | Kilian Ruminski Javier Celis-Gutierrez Javier Celis-Gutierrez Nicolas Jarmuzynski Nicolas Jarmuzynski Emilie Maturin Stephane Audebert Marie Malissen Marie Malissen Luc Camoin Guillaume Voisinne Bernard Malissen Bernard Malissen Romain Roncagalli Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway Frontiers in Immunology TCR SLP76 GRB2-family adaptors mass spectrometry T cell signaling |
| title | Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway |
| title_full | Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway |
| title_fullStr | Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway |
| title_full_unstemmed | Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway |
| title_short | Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway |
| title_sort | mapping the slp76 interactome in t cells lacking each of the grb2 family adaptors reveals molecular plasticity of the tcr signaling pathway |
| topic | TCR SLP76 GRB2-family adaptors mass spectrometry T cell signaling |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1139123/full |
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