title: Galanin receptor-1 modulates 5-hydroxtryptamine-1A signaling via heterodimerization.
abstract: 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.
authors.affiliation: Department of Neuroscience, Karolinska Institutet. Retzius väg 8, 17177 Stockholm, Sweden. Dasiel.Borroto-Escuela@ki.se
authors.forename: Dasiel O
authors.initials: DO
authors.lastname: Borroto-Escuela
authors.forename: Manuel
authors.initials: M
authors.lastname: Narvaez
authors.forename: Daniel
authors.initials: D
authors.lastname: Marcellino
authors.forename: Concepción
authors.initials: C
authors.lastname: Parrado
authors.forename: José Angel
authors.initials: JA
authors.lastname: Narvaez
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Tarakanov
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Agnati
authors.forename: Zaida
authors.initials: Z
authors.lastname: Díaz-Cabiale
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D002460:Cell Line; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D055503:Protein Multimerization; D044091:Receptor, Galanin, Type 1 / Q000235:genetics / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D044091:Receptor, Galanin, Type 1; D044282:Receptor, Serotonin, 5-HT1A; D008156:Luciferases