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Chemokine receptor CCR2 undergoes transportin1‐dependent nuclear translocation
Author(s) -
Favre Nicolas,
Camps Montserrat,
Arod Christian,
Chabert Christian,
Rommel Christian,
Pasquali Christian
Publication year - 2008
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200800211
Subject(s) - ccr2 , chemokine receptor , microbiology and biotechnology , internalization , ccr1 , receptor , g protein coupled receptor , cxc chemokine receptors , chemokine , biology , signal transduction , chemistry , biochemistry
Chemokines (CCs) are small chemoattractant cytokines involved in a wide variety of biological and pathological processes. Released by cells in the milieu, and extracellular matrix and activating signalling cascades upon binding to specific G protein‐coupled receptors (GPCRs), they trigger many cellular events. In various pathologies, CCs are directly responsible for excessive recruitment of leukocytes to inflammatory sites and recent studies using chemokine receptor (CCR) antagonists permitted these molecules to reach the market for medical use. While interaction of CCs with their receptors has been extensively documented, downstream GPCR signalling cascades triggered by CC are less well understood. Given the pivotal role of chemokine receptor 2 (CCR2) in monocyte recruitment, activation and differentiation and its implication in several autoimmune‐inflammatory pathologies, we searched for potential new CCR2‐interacting proteins by engineering a modified CCR2 that we used as bait. Herein, we show the direct interaction of CCR2 with transportin1 (TRN1), which we demonstrate is followed by CCR2 receptor internalization. Further characterization of this novel interaction revealed that TRN1‐binding to CCR2 increased upon time in agonist treated cells and promotes its nuclear translocation in a TRN1‐dependent manner. Finally, we provide evidence that following translocation, the receptor localizes at the outer edge of the nuclear envelope where it is finally released from TRN1.