PMID- 25053617
OWN - NLM
STAT- MEDLINE
DCOM- 20150102
LR  - 20161125
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 28
IP  - 10
DP  - 2014 Oct
TI  - The chemokine CXC4 and CC2 receptors form homo- and heterooligomers that can 
      engage their signaling G-protein effectors and betaarrestin.
PG  - 4509-23
LID - 10.1096/fj.13-242446 [doi]
AB  - G-protein-coupled receptors have been shown to assemble at least as dimers early 
      in the biosynthetic path, but some evidence suggests that they can also form 
      larger oligomeric complexes. Using the human chemokine receptors CXCR4 and CCR2 
      as models, we directly probed the existence of higher order homo- and 
      heterooligomers in human embryonic kidney cells. Combining bimolecular 
      fluorescence and luminescence complementation (BiFC, BiLC) with bioluminescence 
      resonance energy transfer (BRET) assays, we show that CXCR4 and CCR2 can assemble 
      as homo- and heterooligomers, forming at least tetramers. Selective activation of 
      CCR2 with the human monocyte chemotactic protein 1 (MCP-1) resulted in 
      trans-conformational rearrangement of the CXCR4 dimer with an EC50 of 19.9 nM, 
      compatible with a CCR2 action. Moreover, MCP-1 promoted the engagement of Galphai1, 
      Galpha13, Galphaz, and betaarrestin2 to the heterooligomer, resulting in calcium signaling 
      that was synergistically potentiated on coactivation of CCR2 and CXCR4, 
      demonstrating that complexes larger than dimers reach the cell surface as 
      functional units. A mutation of CXCR4 (N119K), which prevents Gi activation, also 
      affects the CCR2-promoted engagement of Galphai1 and betaarrestin2 by the 
      heterooligomer, supporting the occurrence of transprotomer regulation. Together, 
      the results demonstrate that homo- and heteromultimeric CXCR4 and CCR2 can form 
      functional signaling complexes that have unique properties.
CI  - (c) FASEB.
FAU - Armando, Sylvain
AU  - Armando S
AD  - Department of Biochemistry, Institute for Research in Immunology and Cancer, and 
      Institut de Genomique Fonctionnelle, Centre National de la Recherche Scientifique 
      (CNRS) Unite Mixte de Recherche (UMR) 5203, Institut National de la Sante et de 
      la Recherche Medicale (INSERM) U661, University of Montpellier 1 and 2, 
      Montpellier, France.
FAU - Quoyer, Julie
AU  - Quoyer J
AD  - Department of Biochemistry, Institute for Research in Immunology and Cancer, and.
FAU - Lukashova, Viktorya
AU  - Lukashova V
AD  - Department of Biochemistry, Institute for Research in Immunology and Cancer, and.
FAU - Maiga, Arhamatoulaye
AU  - Maiga A
AD  - Department of Biochemistry, Institute for Research in Immunology and Cancer, and.
FAU - Percherancier, Yann
AU  - Percherancier Y
AD  - Department of Biochemistry, Institute for Research in Immunology and Cancer, and.
FAU - Heveker, Nikolaus
AU  - Heveker N
AD  - Department of Biochemistry, Research Centre/Hopital Sainte-Justine, Universite de 
      Montreal, Montreal, Quebec, Canada; and.
FAU - Pin, Jean-Philippe
AU  - Pin JP
AD  - Institut de Genomique Fonctionnelle, Centre National de la Recherche Scientifique 
      (CNRS) Unite Mixte de Recherche (UMR) 5203, Institut National de la Sante et de 
      la Recherche Medicale (INSERM) U661, University of Montpellier 1 and 2, 
      Montpellier, France.
FAU - Prezeau, Laurent
AU  - Prezeau L
AD  - Institut de Genomique Fonctionnelle, Centre National de la Recherche Scientifique 
      (CNRS) Unite Mixte de Recherche (UMR) 5203, Institut National de la Sante et de 
      la Recherche Medicale (INSERM) U661, University of Montpellier 1 and 2, 
      Montpellier, France.
FAU - Bouvier, Michel
AU  - Bouvier M
AD  - Department of Biochemistry, Institute for Research in Immunology and Cancer, and 
      michel.bouvier@umontreal.ca.
LA  - eng
GR  - CTP79848/Canadian Institutes of Health Research/Canada
GR  - MOP11215/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140722
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Arrestins)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (GTP-Binding Protein alpha Subunits)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (beta-Arrestins)
SB  - IM
MH  - Arrestins/*metabolism
MH  - Chemokine CCL2/*metabolism
MH  - GTP-Binding Protein alpha Subunits/*metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Protein Binding
MH  - Protein Multimerization
MH  - Receptors, CCR2/*metabolism
MH  - Receptors, CXCR4/genetics/*metabolism
MH  - *Signal Transduction
MH  - beta-Arrestins
OTO - NOTNLM
OT  - GPCR
OT  - allosteric regulation
OT  - complex formation
OT  - protein complementation assays
OT  - resonance energy transfer
OT  - transactivation
EDAT- 2014/07/24 06:00
MHDA- 2015/01/03 06:00
CRDT- 2014/07/24 06:00
PHST- 2014/07/24 06:00 [entrez]
PHST- 2014/07/24 06:00 [pubmed]
PHST- 2015/01/03 06:00 [medline]
AID - fj.13-242446 [pii]
AID - 10.1096/fj.13-242446 [doi]
PST - ppublish
SO  - FASEB J. 2014 Oct;28(10):4509-23. doi: 10.1096/fj.13-242446. Epub 2014 Jul 22.