Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Involvement of Corticotropin-releasing Factor Receptor 2β in Differentiation of Dopaminergic MN9D Cells

  • Jin, Tae-Eun (Department of Physiology, Sungkyunkwan University, School of Medicine and Center For Molecular Medicine, Samsung Biomedical Research Institute) ;
  • Jang, Miae (Department of Physiology, Sungkyunkwan University, School of Medicine and Center For Molecular Medicine, Samsung Biomedical Research Institute) ;
  • Kim, Hyunjung (Department of Physiology, Sungkyunkwan University, School of Medicine and Center For Molecular Medicine, Samsung Biomedical Research Institute) ;
  • Choi, Yu Mi (Department of Physiology, Sungkyunkwan University, School of Medicine and Center For Molecular Medicine, Samsung Biomedical Research Institute) ;
  • Cho, Hana (Department of Physiology, Sungkyunkwan University, School of Medicine and Center For Molecular Medicine, Samsung Biomedical Research Institute) ;
  • Chung, Sungkwon (Department of Physiology, Sungkyunkwan University, School of Medicine and Center For Molecular Medicine, Samsung Biomedical Research Institute) ;
  • Park, Myoung Kyu (Department of Physiology, Sungkyunkwan University, School of Medicine and Center For Molecular Medicine, Samsung Biomedical Research Institute)
  • Received : 2007.11.27
  • Accepted : 2008.04.14
  • Published : 2008.09.30
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Abstract

Corticotropin releasing factor (CRF) mediates various responses to stress through CRF receptors 1 and 2. CRF receptor 2 has two forms, $2{\alpha}$ and $2{\beta}$ each of which appears to have distinct roles. Here we used dopaminergic neuron-derived MN9D cells to investigate the function of CRF receptor 2 in dopamine neurons. We found that n-butyrate, a histone deacetylase inhibitor, induced MN9D cell differentiation and increased gene expression of all CRF receptors. CRF receptor $2{\beta}$ was minimally expressed in MN9D cells; however, its expression dramatically increased during differentiation. CRF receptor $2{\beta}$ expression levels appeared to correlate with neurite outgrowth, suggesting CRF receptor $2{\beta}$ involvement in neuronal differentiation. To validate this statement, we made a CRF receptor $2{\beta}$-overexpressing $MN9D/CRFR2{\beta}$ stable cell line. This cell line showed robust neurite outgrowth and GAP43 overexpression, together with MEK and ERK activation, suggesting MN9D cell neuronal differentiation. From these results, we conclude that CRF receptor $2{\beta}$ plays an important role in MN9D cell differentiation by activating the MEK/ERK signaling pathway.

Keywords

Acknowledgement

Supported by : Korea Ministry of Science and Technology, Korea Science and Engineering Foundation

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