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Apelin receptor homodimer-oligomers revealed by single-molecule imaging and novel G protein-dependent signaling
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Cai, Xin, Bai, Bo, Zhang, Rumin, Wang, Chunmei and Chen, Jing (2017) Apelin receptor homodimer-oligomers revealed by single-molecule imaging and novel G protein-dependent signaling. Scientific Reports, 7 . 40335 . doi:10.1038/srep40335 ISSN 2045-2322.
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WRAP-apelin-receptor-homodimeroligomers-revealed-novel-Chen-2017.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2878Kb) | Preview |
Official URL: http://doi.org/10.1038/srep40335
Abstract
The apelin receptor (APJ) belongs to family A of the G protein-coupled receptors (GPCRs) and is a potential pharmacotherapeutic target for heart failure, hypertension, and other cardiovascular diseases. There is evidence APJ heterodimerizes with other GPCRs; however, the existence of APJ homodimers and oligomers remains to be investigated. Here, we measured APJ monomer-homodimer-oligomer interconversion by monitoring APJ dynamically on cells and compared their proportions, spatial arrangement, and mobility using total internal reflection fluorescence microscopy, resonance energy transfer, and proximity biotinylation. In cells with <0.3 receptor particles/μm2, approximately 60% of APJ molecules were present as dimers or oligomers. APJ dimers were present on the cell surface in a dynamic equilibrium with constant formation and dissociation of receptor complexes. Furthermore, we applied interference peptides and MALDI-TOF mass spectrometry to confirm APJ homo-dimer and explore the dimer-interfaces. Peptides corresponding to transmembrane domain (TMD)1, 2, 3, and 4, but not TMD5, 6, and 7, disrupted APJ dimerization. APJ mutants in TMD1 and TMD2 also decreased bioluminescence resonance energy transfer of APJ dimer. APJ dimerization resulted in novel functional characteristics, such as a distinct G-protein binding profile and cell responses after agonist stimulation. Thus, dimerization may serve as a unique mechanism for fine-tuning APJ-mediated functions.
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | Q Science > QP Physiology | ||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||||||||
| SWORD Depositor: | Library Publications Router | ||||||||||||
| Library of Congress Subject Headings (LCSH): | G proteins -- Receptors, Homeostasis, Anxiety, Heart -- Diseases, Metabolism -- Disorders | ||||||||||||
| Journal or Publication Title: | Scientific Reports | ||||||||||||
| Publisher: | Nature Publishing Group | ||||||||||||
| ISSN: | 2045-2322 | ||||||||||||
| Official Date: | 16 January 2017 | ||||||||||||
| Dates: |
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| Volume: | 7 | ||||||||||||
| Article Number: | 40335 | ||||||||||||
| DOI: | 10.1038/srep40335 | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||
| Date of first compliant deposit: | 21 February 2018 | ||||||||||||
| Date of first compliant Open Access: | 21 February 2018 | ||||||||||||
| RIOXX Funder/Project Grant: |
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