Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Targets Down Syndrome Candidate Region 1 (DSCR1/RCAN1) to control Neuronal Differentiation |
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| Authors: | Eun Hye Lee Seon Sook Kim Seul Lee Kwan-Hyuck Baek Su Ryeon Seo |
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| Institution: | From the ‡Department of Molecular Bioscience, College of Biomedical Science, and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea and ;the §Department of Molecular and Cellular Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi 440-746, Republic of Korea |
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| Abstract: | Pituitary adenylate cyclase-activating peptide (PACAP) is a neurotrophic peptide involved in a wide range of nervous functions, including development, differentiation, and survival, and various aspects of learning and memory. Here we report that PACAP induces the expression of regulator of calcineurin 1 (RCAN1, also known as DSCR1), which is abnormally expressed in the brains of Down syndrome patients. Increased RCAN1 expression is accompanied by activation of the PKA-cAMP response element-binding protein pathways. EMSA and ChIP analyses demonstrate the presence of a functional cAMP response element in the RCAN1 promoter. Moreover, we show that PACAP-dependent neuronal differentiation is significantly disturbed by improper RCAN1 expression. Our data provide the first evidence of RCAN1, a Down syndrome-related gene, as a novel target for control of the neurotrophic function of PACAP. |
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| Keywords: | cAMP response element-binding protein (CREB) differentiation neuron neuropeptide PKA DSCR1 PACAP RCAN1 |
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