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

Science signaling (2020-02-13)
Camille N Pujol, Vincent Dupuy, Martial Séveno, Leonie Runtz, Joël Bockaert, Philippe Marin, Séverine Chaumont-Dubel
ABSTRACT

The serotonin (5-hydroxytrypatmine) receptor 5-HT6 (5-HT6R) has emerged as a promising target to alleviate the cognitive symptoms of neurodevelopmental diseases. We previously demonstrated that 5-HT6R finely controls key neurodevelopmental steps, including neuronal migration and the initiation of neurite growth, through its interaction with cyclin-dependent kinase 5 (Cdk5). Here, we showed that 5-HT6R recruited G protein-regulated inducer of neurite outgrowth 1 (GPRIN1) through a Gs-dependent mechanism. Interactions between the receptor and either Cdk5 or GPRIN1 occurred sequentially during neuronal differentiation. The 5-HT6R-GPRIN1 interaction enhanced agonist-independent, receptor-stimulated cAMP production without altering the agonist-dependent response in NG108-15 neuroblastoma cells. This interaction also promoted neurite extension and branching in NG108-15 cells and primary mouse striatal neurons through a cAMP-dependent protein kinase A (PKA)-dependent mechanism. This study highlights the complex allosteric modulation of GPCRs by protein partners and demonstrates how dynamic interactions between GPCRs and their protein partners can control the different steps of highly coordinated cellular processes, such as dendritic tree morphogenesis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
牛血清白蛋白 来源于牛血清, lyophilized powder, ≥96% (agarose gel electrophoresis)
Sigma-Aldrich
DPX封片剂用于组织学, slide mounting medium
Sigma-Aldrich
p-Xylene-bis(N-pyridinium bromide), ≥95% (TLC)
Sigma-Aldrich
Anti-Gsα-Subunit, C-Terminal (385-394) Rabbit pAb, liquid, Calbiochem®
BRAND® 96孔微量板,U形底, round bottom, non-sterile