Identification and functional characterization of arginine vasopressin receptor 1A : atypical chemokine receptor 3 heteromers in vascular smooth muscle
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 α1-adrenoceptors. Here, we show that ACKR3 also regulates arginine vasopressin receptor (AVPR)1A. We ob...
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| Format: | Article |
| Language: | English |
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The Royal Society
2018-01-01
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| Series: | Open Biology |
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| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170207 |
| _version_ | 1818257420765364224 |
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| author | Lauren J. Albee Heather M. LaPorte Xianlong Gao Jonathan M. Eby You-Hong Cheng Amanda M. Nevins Brian F. Volkman Vadim Gaponenko Matthias Majetschak |
| author_facet | Lauren J. Albee Heather M. LaPorte Xianlong Gao Jonathan M. Eby You-Hong Cheng Amanda M. Nevins Brian F. Volkman Vadim Gaponenko Matthias Majetschak |
| author_sort | Lauren J. Albee |
| collection | DOAJ |
| description | 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 α1-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 β-arrestin 2 recruitment to AVPR1A and ACKR3. While ACKR3 activation failed to cross-recruit β-arrestin 2 to AVPR1A, the presence of ACKR3 reduced the efficacy of aVP-induced β-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. |
| first_indexed | 2024-12-12T17:43:22Z |
| format | Article |
| id | doaj.art-b609b1fd6eb74be993ae0575e000b79d |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-12-12T17:43:22Z |
| publishDate | 2018-01-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-b609b1fd6eb74be993ae0575e000b79d2022-12-22T00:17:01ZengThe Royal SocietyOpen Biology2046-24412018-01-018110.1098/rsob.170207170207Identification and functional characterization of arginine vasopressin receptor 1A : atypical chemokine receptor 3 heteromers in vascular smooth muscleLauren J. AlbeeHeather M. LaPorteXianlong GaoJonathan M. EbyYou-Hong ChengAmanda M. NevinsBrian F. VolkmanVadim GaponenkoMatthias MajetschakRecent 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 α1-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 β-arrestin 2 recruitment to AVPR1A and ACKR3. While ACKR3 activation failed to cross-recruit β-arrestin 2 to AVPR1A, the presence of ACKR3 reduced the efficacy of aVP-induced β-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.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170207vasoconstrictionvasopressorarginine vasopressincxcl11cxcl12ubiquitin |
| spellingShingle | Lauren J. Albee Heather M. LaPorte Xianlong Gao Jonathan M. Eby You-Hong Cheng Amanda M. Nevins Brian F. Volkman Vadim Gaponenko Matthias Majetschak Identification and functional characterization of arginine vasopressin receptor 1A : atypical chemokine receptor 3 heteromers in vascular smooth muscle Open Biology vasoconstriction vasopressor arginine vasopressin cxcl11 cxcl12 ubiquitin |
| title | Identification and functional characterization of arginine vasopressin receptor 1A : atypical chemokine receptor 3 heteromers in vascular smooth muscle |
| title_full | Identification and functional characterization of arginine vasopressin receptor 1A : atypical chemokine receptor 3 heteromers in vascular smooth muscle |
| title_fullStr | Identification and functional characterization of arginine vasopressin receptor 1A : atypical chemokine receptor 3 heteromers in vascular smooth muscle |
| title_full_unstemmed | Identification and functional characterization of arginine vasopressin receptor 1A : atypical chemokine receptor 3 heteromers in vascular smooth muscle |
| title_short | Identification and functional characterization of arginine vasopressin receptor 1A : atypical chemokine receptor 3 heteromers in vascular smooth muscle |
| title_sort | identification and functional characterization of arginine vasopressin receptor 1a atypical chemokine receptor 3 heteromers in vascular smooth muscle |
| topic | vasoconstriction vasopressor arginine vasopressin cxcl11 cxcl12 ubiquitin |
| url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.170207 |
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