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β‐arrestin‐1 mediates the TCR ‐triggered re‐routing of distal receptors to the immunological synapse by a PKC ‐mediated mechanism
Author(s) -
FernándezArenas Elena,
Calleja Enrique,
MartínezMartín Nadia,
Gharbi Severine I,
Navajas Rosana,
GarcíaMedel Noel,
Penela Petronila,
Alcamí Antonio,
Mayor Federico,
Albar Juan P,
Alarcón Balbino
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/embj.201386022
Subject(s) - t cell receptor , immunological synapse , microbiology and biotechnology , biology , internalization , downregulation and upregulation , chemokine receptor , signal transduction , receptor , arrestin , phosphorylation , c c chemokine receptor type 6 , crosstalk , t cell , g protein coupled receptor , chemokine , immunology , immune system , biochemistry , physics , gene , optics
T‐cell receptors ( TCR ) recognize their antigen ligand at the interface between T cells and antigen‐presenting cells, known as the immunological synapse ( IS ). The IS provides a means of sustaining the TCR signal which requires the continual supply of new TCR s. These are endocytosed and redirected from distal membrane locations to the IS . In our search for novel cytoplasmic effectors, we have identified β‐arrestin‐1 as a ligand of non‐phosphorylated resting TCR s. Using dominant‐negative and knockdown approaches we demonstrate that β‐arrestin‐1 is required for the internalization and downregulation of non‐engaged bystander TCR s. Furthermore, TCR triggering provokes the β‐arrestin‐1‐mediated downregulation of the G‐protein coupled chemokine receptor CXCR 4, but not of other control receptors. We demonstrate that β‐arrestin‐1 recruitment to the TCR , and bystander TCR and CXCR 4 downregulation, are mechanistically mediated by the TCR ‐triggered PKC ‐mediated phosphorylation of β‐arrestin‐1 at Ser163. This mechanism allows the first triggered TCR s to deliver a stop migration signal, and to promote the internalization of distal TCR s and CXCR 4 and their translocation to the IS . This receptor crosstalk mechanism is critical to sustain the TCR signal.