5-HT1A and 5-HT2B receptor interaction and co-clustering regulates serotonergic neuron excitability - Archive ouverte HAL Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2023

5-HT1A and 5-HT2B receptor interaction and co-clustering regulates serotonergic neuron excitability

Imane Moutkine
Xavier Marques
Marion Russeau
Corentin Le Magueresse
Anne Roumier
Sabine Lévi
Luc Maroteaux

Résumé

Many psychiatric diseases including depression, schizophrenia and anxiety have been associated with serotonin (5-HT) signaling dysfunction. We previously showed that the 5-HT 2B receptor was expressed by 5-HT neurons together with 5-HT 1A receptors. Whether 5-HT 2B and 5-HT 1A receptors interact and the functional consequences of this putative interaction are unknown. Using co-immunoprecipitation, BRET, confocal and super-resolution microscopy in hippocampal cultured neurons, we found that 5-HT 1A and 5-HT 2B receptors form heterodimers and co-cluster at the surface of dendrites. The 5-HT 2B receptor cell-surface expression was reduced and the clusters were redistributed upon expression of the 5-HT 1A receptor suggesting functional interactions between the two receptors. Furthermore, the expression of the 5-HT 2B receptor prevented the 5-HT 1A receptor agonist-induced internalization, whereas the presence of the 5-HT 1A receptor mimicked the effect of the stimulation of the 5-HT 2B receptor on its surface expression. These data demonstrate a direct crosstalk between 5-HT 1A and 5-HT 2B receptors. To investigate the functional impact of this interaction in-vivo, we assessed 5-HT neuron excitability from mice lacking 5-HT 2B receptors in 5-HT neurons. We found upon 5-HT 1A receptor stimulation that the firing activity of 5-HT neurons was increased in the absence of 5-HT 2B receptors and decreased in its presence through regulation of SK channels, thus demonstrating the functional significance of these receptor interactions.
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Dates et versions

hal-03944988 , version 1 (18-01-2023)

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Amina Benhadda, Célia Delhaye, Imane Moutkine, Xavier Marques, Marion Russeau, et al.. 5-HT1A and 5-HT2B receptor interaction and co-clustering regulates serotonergic neuron excitability. 2023. ⟨hal-03944988⟩
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