Unknown

Dataset Information

0

Identification and functional characterization of arginine vasopressin receptor 1A : atypical chemokine receptor 3 heteromers in vascular smooth muscle.


ABSTRACT: Recent observations suggest that atypical chemokine receptor (ACKR)3 and chemokine (C-X-C motif) receptor (CXCR)4 regulate human vascular smooth muscle function through hetero-oligomerization with ?1-adrenoceptors. Here, we show that ACKR3 also regulates arginine vasopressin receptor (AVPR)1A. We observed that ACKR3 agonists inhibit arginine vasopressin (aVP)-induced inositol trisphosphate (IP3) production in human vascular smooth muscle cells (hVSMCs) and antagonize aVP-mediated constriction of isolated arteries. Proximity ligation assays, co-immunoprecipitation and bioluminescence resonance energy transfer experiments suggested that recombinant and endogenous ACKR3 and AVPR1A interact on the cell surface. Interference with ACKR3 : AVPR1A heteromerization using siRNA and peptide analogues of transmembrane domains of ACKR3 abolished aVP-induced IP3 production. aVP stimulation resulted in ?-arrestin 2 recruitment to AVPR1A and ACKR3. While ACKR3 activation failed to cross-recruit ?-arrestin 2 to AVPR1A, the presence of ACKR3 reduced the efficacy of aVP-induced ?-arrestin 2 recruitment to AVPR1A. AVPR1A and ACKR3 co-internalized upon agonist stimulation in hVSMC. These data suggest that AVPR1A : ACKR3 heteromers are constitutively expressed in hVSMC, provide insights into molecular events at the heteromeric receptor complex, and offer a mechanistic basis for interactions between the innate immune and vasoactive neurohormonal systems. Our findings suggest that ACKR3 is a regulator of vascular smooth muscle function and a possible drug target in diseases associated with impaired vascular reactivity.

SUBMITTER: Albee LJ 

PROVIDER: S-EPMC5795052 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Identification and functional characterization of arginine vasopressin receptor 1A : atypical chemokine receptor 3 heteromers in vascular smooth muscle.

Albee Lauren J LJ   LaPorte Heather M HM   Gao Xianlong X   Eby Jonathan M JM   Cheng You-Hong YH   Nevins Amanda M AM   Volkman Brian F BF   Gaponenko Vadim V   Majetschak Matthias M  

Open biology 20180101 1


Recent observations suggest that atypical chemokine receptor (ACKR)3 and chemokine (C-X-C motif) receptor (CXCR)4 regulate human vascular smooth muscle function through hetero-oligomerization with α<sub>1</sub>-adrenoceptors. Here, we show that ACKR3 also regulates arginine vasopressin receptor (AVPR)1A. We observed that ACKR3 agonists inhibit arginine vasopressin (aVP)-induced inositol trisphosphate (IP<sub>3</sub>) production in human vascular smooth muscle cells (hVSMCs) and antagonize aVP-me  ...[more]

Similar Datasets

| S-EPMC8224933 | biostudies-literature
| S-EPMC5306277 | biostudies-literature
| S-EPMC5404026 | biostudies-literature
| S-EPMC5586474 | biostudies-literature
| S-EPMC7864378 | biostudies-literature
| S-EPMC3080300 | biostudies-literature
| S-EPMC10265011 | biostudies-literature
| S-EPMC5745408 | biostudies-literature
| S-EPMC1572618 | biostudies-literature
| S-EPMC6970191 | biostudies-literature