KMID : 0578320170400070495
|
|
Molecules and Cells 2017 Volume.40 No. 7 p.495 ~ p.502
|
|
5-Hydroxytryptamine 6 Receptor (5-HT6R)-Mediated Morphological Changes via RhoA-Dependent Pathways
|
|
Rahman Ataur
Kim Han-Na Lee Kang-Ho Yun Hyung-Mun Hong Jung-Hwa Kim Young-Jae Choo Hyun-Ah Park Mi-Kyoung Rhim Hye-Whon
|
|
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.
|
|
KEYWORD
|
|
5-HT6R, dendritic protrusions, live-cell imaging, morphology, serotonin, RhoA-GTP
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|
|