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Renner, Ute; Zeug, Andre; Woehler, Andrew; Niebert, Markus; Dityatev, Alexander; Dityateva, Galina; Gorinski, Nataliya; Guseva, Daria; Abdel-Galil, Dalia; Fröhlich, Matthias; Döring, Frank; Wischmeyer, Erhard; Richter, Diethelm W.; Neher, Erwin; Ponimaskin, Evgeni G.

Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially regulates receptor signalling and trafficking

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  • Medientyp: E-Artikel
  • Titel: Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially regulates receptor signalling and trafficking
  • Beteiligte: Renner, Ute; Zeug, Andre; Woehler, Andrew; Niebert, Markus; Dityatev, Alexander; Dityateva, Galina; Gorinski, Nataliya; Guseva, Daria; Abdel-Galil, Dalia; Fröhlich, Matthias; Döring, Frank; Wischmeyer, Erhard; Richter, Diethelm W.; Neher, Erwin; Ponimaskin, Evgeni G.
  • Erschienen: The Company of Biologists, 2012
  • Erschienen in: Journal of Cell Science
  • Sprache: Englisch
  • DOI: 10.1242/jcs.101337
  • ISSN: 1477-9137; 0021-9533
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>Serotonin receptors 5-HT1A and 5-HT7 are highly co-expressed in brain regions implicated in depression. However, their functional interaction has not been established. In the present study we show that 5-HT1A and 5-HT7 receptors form heterodimers both in vitro and in vivo. Foerster resonance energy transfer-based assays revealed that, in addition to heterodimers, homodimers composed either by 5-HT1A or 5-HT7 receptors together with monomers co-exist in cells. The highest affinity to form the complex was obtained for the 5-HT7-5-HT7 homodimers, followed by the 5-HT7-5-HT1A heterodimers and 5-HT1A-5-HT1A homodimers. Functionally, heterodimerization decreases 5-HT1A receptor-mediated activation of Gi-protein without affecting 5-HT7 receptor-mediated signalling. Moreover, heterodimerization markedly decreases the ability of the 5-HT1A receptor to activate G-protein gated inwardly rectifying potassium channels in a heterologous system. The inhibitory effect on such channels was also preserved in hippocampal neurons, demonstrating a physiological relevance of heteromerization in vivo. In addition, heterodimerization is critically involved in initiation of the serotonin-mediated 5-HT1A receptor internalization and also enhances the ability of the 5-HT1A receptor to activate the mitogen-activated protein kinases. Finally, we found that production of 5-HT7 receptors in hippocampus continuously decreases during postnatal development, indicating that the relative concentration of 5-HT1A-5-HT7 heterodimers and, consequently, their functional importance undergoes pronounced developmental changes.</jats:p>
  • Zugangsstatus: Freier Zugang