5-Hydroxytryptamine 6 Receptor (5-HT6R)-Mediated Morphological Changes via RhoA-Dependent Pathways

Authors
Rahman, Md. AtaurKim, HannaLee, Kang HoYun, Hyung-MunHong, Jung-HwaKim, YoungjaeChoo, HyunahPark, MikyoungRhim, Hyewhon
Issue Date
2017-07
Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
Citation
MOLECULES AND CELLS, v.40, no.7, pp.495 - 502
Abstract
The 5-HT6R has been considered as an attractive therapeutic target in the brain due to its exclusive expression in the brain. However, the mechanistic linkage between 5-HT(6)Rs and brain functions remains poorly understood. Here, we examined the effects of 5-HT6R-mediated cell morphological changes using immunocytochemistry, Western blot, and live-cell imaging assays. Our results showed that the activation of 5-HT(6)Rs caused morphological changes and increased cell surface area in HEK293 cells expressing 5-HT(6)Rs. Treatment with 5-HT specifically increased RhoA-GTP activity without affecting other Rho family proteins, such as Rac1 and Cdc42. Furthermore, live-cell imaging in hippocampal neurons revealed that activation of 5-HT(6)Rs using a selective agonist, ST1936, increased the density and size of dendritic protrusions along with the activation of RhoA-GTP activity and that both effects were blocked by pretreatment with a selective 5-HT6R antagonist, SB258585. Taken together, our results show that 5-HT6R plays an important role in the regulation of cell morphology via a RhoA-dependent pathway in mammalian cell lines and primary neurons.
Keywords
PHYSICAL INTERACTION; DENDRITIC SPINES; 5-HT6 RECEPTORS; SMALL GTPASES; SEROTONIN; PLASTICITY; ACTIVATION; MECHANISM; NEURONS; PHYSICAL INTERACTION; DENDRITIC SPINES; 5-HT6 RECEPTORS; SMALL GTPASES; SEROTONIN; PLASTICITY; ACTIVATION; MECHANISM; NEURONS; 5-HT6R; dendritic protrusions; live-cell imaging; morphology; serotonin; RhoA-GTP
ISSN
1016-8478
URI
https://pubs.kist.re.kr/handle/201004/122572
DOI
10.14348/molcells.2017.0080
Appears in Collections:
KIST Article > 2017
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