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, M. Palkóvits, Kjell Fuxe

Research output: Contribution to journalArticle

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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

Fingerprint

Fibroblast Growth Factor 2
Serotonin 5-HT1 Receptor Agonists
Modulation
8-Hydroxy-2-(di-n-propylamino)tetralin
Receptor, Serotonin, 5-HT1A
Arrestin
Protein Subunits
Antidepressive Agents
Assays
Brain
Serotonin
Chemical activation
Proteins
hydroxide ion

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

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Dynamic modulation of FGFR1-5-HT1A heteroreceptor complexes. Agonist treatment enhances participation of FGFR1 and 5-HT1A homodimers and recruitment of β-arrestin2. / Borroto-Escuela, Dasiel O.; Corrales, Fidel; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F.; Palkóvits, M.; Fuxe, Kjell.

In: Biochemical and Biophysical Research Communications, Vol. 441, No. 2, 15.11.2013, p. 387-392.

Research output: Contribution to journalArticle

Borroto-Escuela, Dasiel O. ; Corrales, Fidel ; Narvaez, Manuel ; Oflijan, Julia ; Agnati, Luigi F. ; Palkóvits, M. ; Fuxe, Kjell. / Dynamic modulation of FGFR1-5-HT1A heteroreceptor complexes. Agonist treatment enhances participation of FGFR1 and 5-HT1A homodimers and recruitment of β-arrestin2. In: Biochemical and Biophysical Research Communications. 2013 ; Vol. 441, No. 2. pp. 387-392.
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AU - Borroto-Escuela, Dasiel O.

AU - Corrales, Fidel

AU - Narvaez, Manuel

AU - Oflijan, Julia

AU - Agnati, Luigi F.

AU - Palkóvits, M.

AU - Fuxe, Kjell

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