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Rab11-FIP3 Regulation of Lck Endosomal Traffic Controls TCR Signal Transduction
- Source :
- Journal of Immunology, Journal of Immunology, 2017, pp.2967-2978. ⟨10.4049/jimmunol.1600671⟩, Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2017, pp.2967-2978. ⟨10.4049/jimmunol.1600671⟩
- Publication Year :
- 2017
- Publisher :
- HAL CCSD, 2017.
-
Abstract
- The role of endosomes in receptor signal transduction is a long-standing question, which remains largely unanswered. The T cell Ag receptor and various components of its proximal signaling machinery are associated with distinct endosomal compartments, but how endosomal traffic affects T cell signaling remains ill-defined. In this article, we demonstrate in human T cells that the subcellular localization and function of the protein tyrosine kinase Lck depends on the Rab11 effector FIP3 (Rab11 family interacting protein-3). FIP3 overexpression or silencing and its ability to interact with Rab11 modify Lck subcellular localization and its delivery to the immunological synapse. Importantly, FIP3-dependent Lck localization controls early TCR signaling events, such as tyrosine phosphorylation of TCRζ, ZAP70, and LAT and intracellular calcium concentration, as well as IL-2 gene expression. Interestingly, FIP3 controls both steady-state and poststimulation phosphotyrosine and calcium levels. Finally, our findings indicate that FIP3 modulates TCR-CD3 cell surface expression via the regulation of steady-state Lck-mediated TCRζ phosphorylation, which in turn controls TCRζ protein levels. This may influence long-term T cell activation in response to TCR-CD3 stimulation. Therefore, our data underscore the importance of finely regulated endosomal traffic in TCR signal transduction and T cell activation leading to IL-2 production.
- Subjects :
- 0301 basic medicine
Immunological Synapses
T-Lymphocytes
T cell
Blotting, Western
Immunology
Receptors, Antigen, T-Cell
Endosomes
[SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Lymphocyte Activation
Polymerase Chain Reaction
Immunological synapse
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
medicine
Humans
Immunology and Allergy
Microscopy, Confocal
Chemistry
ZAP70
T-cell receptor
Tyrosine phosphorylation
I-kappa B Kinase
Cell biology
Protein Transport
030104 developmental biology
medicine.anatomical_structure
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
rab GTP-Binding Proteins
Gene Knockdown Techniques
Phosphorylation
Signal transduction
Tyrosine kinase
Signal Transduction
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 00221767 and 15506606
- Database :
- OpenAIRE
- Journal :
- Journal of Immunology, Journal of Immunology, 2017, pp.2967-2978. ⟨10.4049/jimmunol.1600671⟩, Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2017, pp.2967-2978. ⟨10.4049/jimmunol.1600671⟩
- Accession number :
- edsair.doi.dedup.....f89c6f42b7661b927e4ac4fb7f6ba32e