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Signaling transduction regulated by 5-hydroxytryptamine 1A receptor and orexin receptor 2 heterodimers
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Wang, Qin-Qin, Wang, Chun-Mei, Cheng, Bao-Hua, Yang, Chun-Qing, Bai, Bo and Chen, Jing (2019) Signaling transduction regulated by 5-hydroxytryptamine 1A receptor and orexin receptor 2 heterodimers. Cellular Signalling, 54 . pp. 46-58. doi:10.1016/j.cellsig.2018.11.014 ISSN 0898-6568.
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WRAP-signaling-transduction-regulated-5-hydroxytryptamine-1A-receptor-orexin-receptor-2-heterodimers-Chen-2019.pdf - Accepted Version - Requires a PDF viewer. Download (2067Kb) | Preview |
Official URL: http://dx.doi.org/10.1016/j.cellsig.2018.11.014
Abstract
As G-protein-coupled receptors (GPCRs), 5-hydroxytryptamine 1A receptor (5-HT1AR) and orexin receptor 2 (OX2R) regulate the levels of the cellular downstream molecules. The heterodimers of different GPCRs play important roles in various of neurological diseases. Moreover, 5-HT1AR and OX2R are involved in the pathogenesis of neurological diseases such as depression with deficiency of hippocampus plasticity. However, the direct interaction of the two receptors remains elusive. In the present study, we firstly demonstrated the heterodimer formation of 5-HT1AR and OX2R. Exchange protein directly activated by cAMP (Epac) cAMP bioluminescence resonance energy transfer (BRET) biosensor analysis revealed that the expression levels of cellular cAMP significantly increased in HEK293T cells transfected with the two receptors compared with the 5-HT1AR group. Additionally, the cellular level of calcium was upregulated robustly in HEK293T cells co-transfected with 5-HT1AR and OX2R group after agonist treatment. Furthermore, western blotting data showed that 5-HT1AR and OX2R heterodimer decreased the levels of phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP-response element-binding protein (CREB). These results not only unraveled the formation of 5-HT1AR and OX2R heterodimer but also suggested that the heterodimer affected the downstream signaling pathway, which will provide new insights into the function of the two receptors in the brain.
Item Type: | Journal Article | ||||||||||||||||||
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Subjects: | Q Science > QH Natural history Q Science > QP Physiology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Cell receptors, G proteins, Nervous system -- Diseases, Depression, Mental, Phosphorylation | ||||||||||||||||||
Journal or Publication Title: | Cellular Signalling | ||||||||||||||||||
Publisher: | Elsevier | ||||||||||||||||||
ISSN: | 0898-6568 | ||||||||||||||||||
Official Date: | February 2019 | ||||||||||||||||||
Dates: |
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Volume: | 54 | ||||||||||||||||||
Page Range: | pp. 46-58 | ||||||||||||||||||
DOI: | 10.1016/j.cellsig.2018.11.014 | ||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||||||||||||
Date of first compliant deposit: | 3 December 2018 | ||||||||||||||||||
Date of first compliant Open Access: | 24 November 2019 | ||||||||||||||||||
RIOXX Funder/Project Grant: |
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