Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 393, Issue 4, Pages 767-772Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2010.02.078
Keywords
Galanin receptor; 5-hydroxtryptamine-1A receptor; Heterodimerization; Receptor-receptor interactions; FRET; Allosteric modulation
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Funding
- Swedish Research Council [04X-715]
- Torsten and Ragnar Soderberg Foundation
- Hjarnfonden and Marianne and Marcus Wallenberg Foundation
- Fundacio la Marato de TV3, Generalitat de Catalunya, Barcelona, Spain
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Previous biochemical, cardiovascular and behavioral work has given evidence for the existence of antagonistic galanin receptor-5-HT1A receptor interactions in the brain. In this study we investigated the existence of GalR1-5-HT1A receptor heteromers and their functional characteristics. In mammalian cells transfected with GFP2-tagged 5-HT1A receptor and YFP-tagged GalR1 receptor, a proximity-based fluorescence resonance energy transfer technique was used and it has been demonstrated that GalR1-5-HT1A receptors heteromerize. Furthermore, signaling by either the mitogen-activated protein kinase (MAPK) or adenylyl cyclase (AC) pathways by these heteromers indicates a trans-inhibition phenomenon through their interacting interface via allosteric mechanisms that block the development of an excessive activation of G(i/o) and an exaggerated inhibition of AC or stimulation of MAPK activity. The presence of these heteromers in the discrete brain regions is postulated based on the existence of GalR-5-HT1A receptor-receptor interactions previously described in the brain and gives rise to explore possible novel therapeutic strategies for treatment of depression by targeting the GalR1-5-HT1A heteromers. (C) 2010 Elsevier Inc. All rights reserved.
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