title: Evidence for the existence of FGFR1-5-HT1A heteroreceptor complexes in the midbrain raphe 5-HT system.
abstract: The ascending midbrain 5-HT neurons known to contain 5-HT1A autoreceptors may be dysregulated in depression due to a reduced trophic support. With in situ proximity ligation assay (PLA) and supported by co-location of the FGFR1 and 5-HT1A immunoreactivities in midbrain raphe 5-HT cells, evidence for the existence of FGFR1-5-HT1A heteroreceptor complexes were obtained in the dorsal and median raphe nuclei of the Sprague-Dawley rat. Their existence in the rat medullary raphe RN33B cell cultures was also established. After combined FGF-2 and 8-OH-DPAT treatment, a marked and significant increase in PLA positive clusters was found in the RN33B cells. Similar results were reached upon coactivation by agonists in HEK293T cells using the Fluorescent Resonance Energy Transfer (FRET) technique resulting in increased FRETmax and reduced FRET50 values. The heteroreceptor complex formation was dependent on TMV of the 5-HT1A receptor since it was blocked by incubation with TMV but not with TMII. Taken together, the 5-HT1A autoreceptors by being recruited into a FGFR1-5-HT1A heteroreceptor complex in the midbrain raphe 5-HT nerve cells may develop a novel function, namely a trophic role in many midbrain 5-HT neuron systems originating from the dorsal and medianus raphe nuclei.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: Dasiel.Borroto.Escuela@ki.se.
authors.forename: Dasiel O
authors.initials: DO
authors.lastname: Borroto-Escuela
authors.affiliation: Department of Physiology, School of Medicine, University of Málaga, Spain. Electronic address: mnarvaez@uma.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Narvaez
authors.affiliation: Lab Animal Models and Cancer Laboratory Anatomy Pathology Program, Institut de Recerca Vall d'Hebron, 08035 Barcelona, Spain. Electronic address: mileidys.perez@vhir.org.
authors.forename: Mileidys
authors.initials: M
authors.lastname: Pérez-Alea
authors.affiliation: Russian Academy of Sciences, St. Petersburg Institute for Informatics and Automation, Saint Petersburg, Russia. Electronic address: tar@iias.spb.su.
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Tarakanov
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: Tony.jimenez-beristain@ki.se.
authors.forename: Antonio
authors.initials: A
authors.lastname: Jiménez-Beristain
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, Laboratory of Molecular Neurobiology, University of Palermo, Palermo, Italy. Electronic address: g.mudo@unipa.it.
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Mudó
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: luigiagnati@tin.it.
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Agnati
authors.affiliation: Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Universitat de Barcelona, Spain. Electronic address: fciruela@ub.edu.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, Laboratory of Molecular Neurobiology, University of Palermo, Palermo, Italy. Electronic address: n.belluardo@unipa.it.
authors.forename: Natale
authors.initials: N
authors.lastname: Belluardo
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: Kjell.Fuxe@ki.se.
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D019281:Dimerization; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D031541:Fluorescence Resonance Energy Transfer; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D066267:Midbrain Raphe Nuclei / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism
chemical_list: D010455:Peptides; D016222:Fibroblast Growth Factor 2; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C496348:FGFR1 protein, human; C496350:Fgfr1 protein, rat; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: Dimerization; Fibroblast growth factor receptor 1; G-protein-coupled receptors; Heteroreceptor complex; Receptor tyrosine kinases; Serotonin receptors