| Title: |
Phosphoinositides regulate the TCR/CD3 complex membrane dynamics and activation |
| Authors: |
Chouaki-Benmansour, Nassima; Ruminski, Kilian; Sartre, Anne-Marie; Phelipot, Marie-Claire; Salles, Audrey; Bergot, Elise; Wu, Ambroise; Chicanne, Gaëtan; Fallet, Mathieu; Brustlein, Sophie; Billaudeau, Cyrille; Formisano, Anthony; Mailfert, Sébastien; Payrastre, Bernard; Marguet, Didier; Brasselet, Sophie; Hamon, Yannick; He, Hai-Tao |
| Contributors: |
Centre d'Immunologie de Marseille - Luminy (CIML); Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Institut des Maladies Métaboliques et Cardiovasculaires (I2MC); Université Toulouse III - Paul Sabatier (UT3); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM); Institut FRESNEL (FRESNEL); Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS); Laboratoire de photonique et de nanostructures (LPN); Centre National de la Recherche Scientifique (CNRS); Centre de Physiopathologie Toulouse Purpan (CPTP); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); This work was supported by institutional grants from INSERM and CNRS and by specific grants from the Agence Nationale de la Recherche (ANR-10-BLAN-1509; ANR-11-LABX-Investissement d’Avenir Labex-INFORM; ANR-10-INBS-04-01 France Bio Imaging; ANR-10-BLAN-1509,ReceptOrient,Observation de l'activation du récepteur des lymphocytes T (TCR) en temps réel: suivi des orientations dynamiques du domaine intracellulaire du complexe récepteur dans les cellules vivantes par imagerie en fluorescence polarisée résolue de temps(2010); ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010) |
| Source: |
ISSN: 2045-2322. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2018 |
| Collection: |
Université Toulouse III - Paul Sabatier: HAL-UPS |
| Subject Terms: |
[SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic |
| Description: |
International audience ; Phosphoinositides (PIs) play important roles in numerous membrane-based cellular activities. However, their involvement in the mechanism of T cell receptor (TCR) signal transduction across the plasma membrane (PM) is poorly defined. Here, we investigate their role, and in particular that of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] in TCR PM dynamics and activity in a mouse T-cell hybridoma upon ectopic expression of a PM-localized inositol polyphosphate-5-phosphatase (Inp54p). We observed that dephosphorylation of PI(4,5)P2 by the phosphatase increased the TCR/CD3 complex PM lateral mobility prior stimulation. The constitutive and antigen-elicited CD3 phosphorylation as well as the antigen-stimulated early signaling pathways were all found to be significantly augmented in cells expressing the phosphatase. Using state-of-the-art biophotonic approaches, we further showed that PI(4,5)P2 dephosphorylation strongly promoted the CD3ε cytoplasmic domain unbinding from the PM inner leaflet in living cells, thus resulting in an increased CD3 availability for interactions with Lck kinase. This could significantly account for the observed effects of PI(4,5)P2 dephosphorylation on the CD3 phosphorylation. Our data thus suggest that PIs play a key role in the regulation of the TCR/CD3 complex dynamics and activation at the PM. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/29563576; PRODINRA: 428683; PUBMED: 29563576; WOS: 000427926500010 |
| DOI: |
10.1038/s41598-018-23109-8 |
| Availability: |
https://hal.science/hal-01920092; https://hal.science/hal-01920092v1/document; https://hal.science/hal-01920092v1/file/s41598-018-23109-8.pdf; https://doi.org/10.1038/s41598-018-23109-8 |
| Rights: |
http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.1326CFB0 |
| Database: |
BASE |