Heteromerization between α1B -adrenoceptor and chemokine (C-C motif) receptor 2 biases α1B -adrenoceptor signaling: Implications for vascular function.
FEBS Lett
; 596(20): 2706-2716, 2022 10.
Article
in En
| MEDLINE
| ID: mdl-35920096
ABSTRACT
Previously, we reported that chemokine (C-C motif) receptor 2 (CCR2) heteromerizes with α1B -adrenoceptor (α1B -AR) in leukocytes, through which α1B -AR controls CCR2. Whether such heteromers are expressed in human vascular smooth muscle cells (hVSMCs) is unknown. Bioluminescence resonance energy transfer confirmed formation of recombinant CCR2α1b -AR heteromers. Proximity ligation assays detected CCR2α1B -AR heteromers in hVSMCs and human mesenteric arteries. CCR2α1B -AR heteromerization per se enhanced α1B -AR-mediated Gαq -coupling. Chemokine (C-C motif) ligand 2 (CCL2) binding to CCR2 inhibited Gαq activation via α1B -AR, cross-recruited ß-arrestin to and induced internalization of α1B -AR in recombinant systems and in hVSMCs. Our findings suggest that CCR2 within CCR2α1B -AR heteromers biases α1B -AR signaling and provide a mechanism for previous observations suggesting a role for CCL2/CCR2 in the regulation of cardiovascular function.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Adrenergic, alpha-1
/
Chemokine CCL2
Limits:
Humans
Language:
En
Journal:
FEBS Lett
Year:
2022
Document type:
Article
Affiliation country:
United States