Involvement of corticotropin-releasing factor receptor 2 beta in differentiation of dopaminergic MN9D cells.
Corticotropin releasing factor (CRF) mediates various responses to stress through CRF receptors 1 and 2. CRF receptor 2 has two forms, 2alpha and 2beta 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 2beta was minimally expressed in MN9D cells; however, its expression dramatically increased during differentiation. CRF receptor 2beta expression levels appeared to correlate with neurite outgrowth, suggesting CRF receptor 2beta involvement in neuronal differentiation. To validate this statement, we made a CRF receptor 2beta-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 2beta plays an important role in MN9D cell differentiation by activating the MEK/ERK signaling pathway.
Department of Physiology, Sungkyunkwan University, School of Medicine and Center For Molecular Medicine, Samsung Biomedical Research Institute, Suwon 440-746, Korea.
Tae-Eun
TE
Jin
Miae
M
Jang
Hyunjung
H
Kim
Yu Mi
YM
Choi
Hana
H
Cho
Sungkwon
S
Chung
Myoung Kyu
MK
Park
D000818:Animals; D002087:Butyrates / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D048430:Cell Shape; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*
D002087:Butyrates; C101531:CRF receptor type 2; D056572:Histone Deacetylase Inhibitors; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D004298:Dopamine