Dynamic modulation of FGFR1-5-HT1A heteroreceptor complexes. Agonist treatment enhances participation of FGFR1 and 5-HT1A homodimers and recruitment of β-arrestin2

Dasiel O. Borroto-Escuela, Fidel Corrales, Manuel Narvaez, Julia Oflijan, Luigi F. Agnati, Miklós Palkovits, Kjell Fuxe

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

New findings show that neurotrophic and antidepressant effects of 5-HT in brain can, in part, be mediated by activation of the 5-HT1A receptor protomer in the hippocampal and raphe FGFR1-5-HT1A heteroreceptor complexes enhancing the FGFR1 signaling. The dynamic agonist modulation of the FGFR1-5-HT1A heteroreceptor complexes and their recruitment of β-arrestin is now determined in cellular models with focus on its impact on 5-HT1AR and FGFR1 homodimerization in the heteroreceptor complexes based on BRET2 assays. The findings show that coagonist treatment with 8-OH-DPAT and FGF2 but not treatment with the 5-HT1A agonist alone markedly increases the BRETmax values and significantly reduces the BRET50 values of 5HT1A homodimerization. The effects of FGF2 or FGF20 with or without the 5-HT1A agonist were also studied on the FGFR1 homodimerization of the heteroreceptor complexes. FGF2 produced a marked and rapid increase in FGFR1 homodimerization which partially declined over a 10 min period. Cotreatment with FGF2 and 5-HT1A agonist blocked this decline in FGFR1 homodimerization. Furthermore, FGF2 alone produced a small increase in the BRET2 signal from the 5-HT1A-β-arrestin2 receptor-protein complex which was additive to the marked effect of 8-OH-DPAT alone. Taken together, the participation of 5-HT1A and FGFR1 homodimers and recruitment of β-arrestin2 was demonstrated in the FGFR1-5-HT1A heteroreceptor complexes upon agonist treatments.

Original languageEnglish
Pages (from-to)387-392
Number of pages6
JournalBiochemical and biophysical research communications
Volume441
Issue number2
DOIs
Publication statusPublished - Nov 15 2013

Keywords

  • Allosteric modulation
  • Bioluminescence resonance energy transfer
  • Fibroblast growth factor receptor 1
  • G-protein-coupled receptors
  • Heterocomplex
  • Homodimerization
  • Protein-protein interactions
  • Receptor tyrosine kinases
  • Serotonin receptors

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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