Research ArticleGPCR SIGNALING

Dynamic interactions of the 5-HT6 receptor with protein partners control dendritic tree morphogenesis

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Science Signaling  11 Feb 2020:
Vol. 13, Issue 618, eaax9520
DOI: 10.1126/scisignal.aax9520

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Taking the time to signal

The serotonin receptor 5-HT6R is a GPCR exclusively found in the nervous system that has emerged as a potential therapeutic target in various neurological disorders. Although preliminary studies suggested that 5-HT6R antagonists have procognitive effects, clinical trials have been disappointing. Pujol et al. analyzed the dynamics of 5-HT6R interactions with other proteins and found that after its previously characterized interaction with and phosphorylation by the kinase Cdk5, the 5-HT6R interacted with GPRIN1, a promoter of neurite extension. These sequential interactions enhanced 5-HT6R constitutive activity, promoting neurite extension and branching in neuroblastoma cells and primary striatal neurons. The GPRIN1–5-HT6R interaction was reduced by 5-HT6R antagonist, suggesting that the dynamic interactions of this receptor are regulated by its conformational state.

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