Molecules and Cells

  • 제40권7호
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  • Pages.495-502
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  • 2017
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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5-Hydroxytryptamine 6 Receptor (5-HT6R)-Mediated Morphological Changes via RhoA-Dependent Pathways

  • Rahman, Md. Ataur (Center for Neuroscience, Korea Institute of Science and Technology) ;
  • Kim, Hanna (Center for Functional Connectomics, Korea Institute of Science and Technology) ;
  • Lee, Kang Ho (Center for Neuroscience, Korea Institute of Science and Technology) ;
  • Yun, Hyung-Mun (Center for Neuroscience, Korea Institute of Science and Technology) ;
  • Hong, Jung-Hwa (Center for Functional Connectomics, Korea Institute of Science and Technology) ;
  • Kim, Youngjae (Center for Neuro-Medicine, Korea Institute of Science and Technology) ;
  • Choo, Hyunah (Center for Neuro-Medicine, Korea Institute of Science and Technology) ;
  • Park, Mikyoung (Center for Functional Connectomics, Korea Institute of Science and Technology) ;
  • Rhim, Hyewhon (Center for Neuroscience, Korea Institute of Science and Technology)
  • 투고 : 2017.05.16
  • 심사 : 2017.05.18
  • 발행 : 2017.07.31
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초록

The $5-HT_6R$ has been considered as an attractive therapeutic target in the brain due to its exclusive expression in the brain. However, the mechanistic linkage between $5-HT_6Rs$ and brain functions remains poorly understood. Here, we examined the effects of $5-HT_6R$-mediated cell morphological changes using immunocytochemistry, Western blot, and live-cell imaging assays. Our results showed that the activation of $5-HT_6Rs$ caused morphological changes and increased cell surface area in HEK293 cells expressing $5-HT_6Rs$. 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 $5-HT_6Rs$ 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 $5-HT_6R$ antagonist, SB258585. Taken together, our results show that $5-HT_6R$ plays an important role in the regulation of cell morphology via a RhoA-dependent pathway in mammalian cell lines and primary neurons.

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참고문헌

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