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

Renner, U., Zeug, A., Woehler, A., Niebert, M., Dityatev, A., Dityateva, G., et al. (2012). Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially regulates receptor signalling and trafficking. Journal of Cell Science, 125(10), 2486-2499. doi:10.1242/jcs.101337.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000F-A828-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-1F24-3
Genre: Journal Article

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 Creators:
Renner, U., Author
Zeug, A., Author
Woehler, A.1, Author              
Niebert, M., Author
Dityatev, A., Author
Dityateva, G., Author
Gorinski, N., Author
Guseva, D., Author
Abdel-Galil, D., Author
Fröhlich, M., Author
Döring, F., Author
Wischmeyer, E., Author
Richter, D. W., Author
Neher, E.1, Author              
Ponimaskin, E. G., Author
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1Emeritus Group of Membrane Biophysics, MPI for Biophysical Chemistry, Max Planck Society, ou_1571137              

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Free keywords: G-protein coupled receptor, Oligomerization, Signal transduction
 Abstract: Serotonin receptors 5-HT 1A and 5-HT 7 are highly coexpressed in brain regions implicated in depression. However, their functional interaction has not been established. In the present study we show that 5-HT 1A and 5-HT 7 receptors form heterodimers both in vitro and in vivo. Foerster resonance energy transfer-based assays revealed that, in addition to heterodimers, homodimers composed either of 5- HT 1A or 5-HT 7 receptors together with monomers coexist in cells. The highest affinity for complex formation was obtained for the 5-HT 7 –5-HT 7 homodimers, followed by the 5-HT 7 –5-HT 1A heterodimers and 5-HT 1A –5-HT 1A homodimers. Functionally, heterodimerization decreases 5-HT 1A -receptor-mediated activation of G i protein without affecting 5-HT 7 -receptor-mediated signalling. Moreover, heterodimerization markedly decreases the ability of the 5-HT 1A 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 crucially involved in initiation of the serotonin-mediated 5-HT 1A receptor internalization and also enhances the ability of the 5-HT 1A receptor to activate the mitogen-activated protein kinases. Finally, we found that production of 5-HT 7 receptors in the hippocampus continuously decreases during postnatal development, indicating that the relative concentration of 5-HT 1A –5-HT 7 heterodimers and, consequently, their functional importance undergoes pronounced developmental changes

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Language(s): eng - English
 Dates: 2012-02-222012-05-15
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1242/jcs.101337
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Title: Journal of Cell Science
Source Genre: Journal
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Pages: - Volume / Issue: 125 (10) Sequence Number: - Start / End Page: 2486 - 2499 Identifier: -