5-Hydroxytryptamine 6 Receptor (5-HT6R)-Mediated Morphological Changes via RhoA-Dependent
Pathways
Md. Ataur Rahman1,8, Hanna Kim2,8, Kang Ho Lee1,3, Hyung-Mun Yun1, Jung-Hwa Hong2,4,
Youngjae Kim5,6, Hyunah Choo5,7, Mikyoung Park2,3, and Hyewhon Rhim1,3,*
1Center for Neuroscience, 2Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul 02792, Korea, 3Department of Neuroscience, Korea University of Science and Technology, Daejeon 34113, Korea, 4Department of Life Sciences,
Korea University, Seoul 02841, Korea, 5Center for Neuro-Medicine, Korea Institute of Science and Technology, Seoul 02792,
Korea, 6Department of Chemistry, Yonsei University, Seoul 03722, Korea, 7Department of Biological Chemistry, Korea University
of Science and Technology, Daejeon 34113, Korea, 8These authors contributed equally to this work.
*Correspondence: hrhim@kist.re.kr
Received May 16, 2017; Accepted May 18, 2017.; Published online June 30, 2017.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit (http://creativecommons.org/licenses/by-nc-sa/3.0/).
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-HT6Rs 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-HT6Rs caused morphological changes and increased cell surface area in HEK293 cells expressing 5-HT6Rs. 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-HT6Rs 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: 5-HT6R, dendritic protrusions, live-cell imaging, morphology, serotonin, RhoA-GTP


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