6533b839fe1ef96bd12a6656

RESEARCH PRODUCT

Evidence for the existence of FGFR1-5-HT1A heteroreceptor complexes in the midbrain raphe 5-HT system.

Antonio Jiménez-beristainFrancisco CiruelaLuigi F. AgnatiKjell FuxeDasiel O. Borroto-escuelaNatale BelluardoGiuseppa MudòManuel NarváezMileidys Pérez-aleaAlexander O. Tarakanov

subject

Malemedicine.medical_specialtySerotoninG-protein-coupled receptorReceptor tyrosine kinaseBiophysicsHeteroreceptor complexProximity ligation assayBiologyHeteroreceptorBiochemistryMidbrainRats Sprague-DawleyG-protein-coupled receptors; Receptor tyrosine kinases; Fibroblast growth factor receptor 1; Serotonin receptors; Heteroreceptor complex; DimerizationInternal medicinemedicineFluorescence Resonance Energy TransferAnimalsHumansReceptor Fibroblast Growth Factor Type 1Serotonin receptorMolecular Biology5-HT receptorNeurons8-Hydroxy-2-(di-n-propylamino)tetralinRapheMidbrain Raphe NucleiCell BiologyFibroblast growth factor receptor 1Cell biologyRatsmedicine.anatomical_structureEndocrinologyHEK293 Cellsnervous systemGene Expression RegulationReceptor Serotonin 5-HT1AAutoreceptorFibroblast Growth Factor 2NeuronRaphe nucleiPeptidesDimerizationProtein Binding

description

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.

yearjournalcountryeditionlanguage
2015-01-01Biochemical and biophysical research communications
10.1016/j.bbrc.2014.11.112https://pubmed.ncbi.nlm.nih.gov/25485703