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

Natale Belluardo, Giuseppa Mudo', Antonio Jiménez-Beristain, Francisco Ciruela, Alexander O. Tarakanov, Mileidys Pérez-Alea, Luigi F. Agnati, Dasiel O. Borroto-Escuela, Manuel Narvaez, Kjell Fuxe

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)489-493
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume456
Publication statusPublished - 2015

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Serotonin
Neurons
Autoreceptors
Mesencephalon
Ligation
Rats
Assays
8-Hydroxy-2-(di-n-propylamino)tetralin
Receptor, Serotonin, 5-HT1A
Energy Transfer
Fibroblast Growth Factor 2
Cell culture
Energy transfer
Sprague Dawley Rats
Cell Culture Techniques
Midbrain Raphe Nuclei
Dorsal Raphe Nucleus

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Cell Biology
  • Molecular Biology
  • Biochemistry

Cite this

Evidence for the existence of FGFR1–5-HT1A heteroreceptor complexes in the midbrain raphe 5-HT system. / Belluardo, Natale; Mudo', Giuseppa; Jiménez-Beristain, Antonio; Ciruela, Francisco; Tarakanov, Alexander O.; Pérez-Alea, Mileidys; Agnati, Luigi F.; Borroto-Escuela, Dasiel O.; Narvaez, Manuel; Fuxe, Kjell.

In: Biochemical and Biophysical Research Communications, Vol. 456, 2015, p. 489-493.

Research output: Contribution to journalArticle

Belluardo, N, Mudo', G, Jiménez-Beristain, A, Ciruela, F, Tarakanov, AO, Pérez-Alea, M, Agnati, LF, Borroto-Escuela, DO, Narvaez, M & Fuxe, K 2015, 'Evidence for the existence of FGFR1–5-HT1A heteroreceptor complexes in the midbrain raphe 5-HT system', Biochemical and Biophysical Research Communications, vol. 456, pp. 489-493.
Belluardo, Natale ; Mudo', Giuseppa ; Jiménez-Beristain, Antonio ; Ciruela, Francisco ; Tarakanov, Alexander O. ; Pérez-Alea, Mileidys ; Agnati, Luigi F. ; Borroto-Escuela, Dasiel O. ; Narvaez, Manuel ; Fuxe, Kjell. / Evidence for the existence of FGFR1–5-HT1A heteroreceptor complexes in the midbrain raphe 5-HT system. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 456. pp. 489-493.
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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.",
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AU - Ciruela, Francisco

AU - Tarakanov, Alexander O.

AU - Pérez-Alea, Mileidys

AU - Agnati, Luigi F.

AU - Borroto-Escuela, Dasiel O.

AU - Narvaez, Manuel

AU - Fuxe, Kjell

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AB - 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.

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