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A Role of CPEB1 in the Modulation of Proliferation and Neuronal Maturation of Rat Primary Neural Progenitor Cells

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Abstract

Cytoplasmic polyadenylation binding protein 1 (CPEB1) is a RNA binding protein, which regulates translation of target mRNAs by regulating polyadenylation status. CPEB1 plays important roles in the regulation of germline cell development by modulating cell cycle progression through the polyadenylation of target mRNAs such as cyclin B1. Similar mechanism is reported in proliferating astrocytes by us, although CPEB1 is involved in the transport of target mRNAs as well as local translation at dendritic spines. In this study, we found the expression of CPEB1 in cultured rat primary neural progenitor cells (NPCs). EGF stimulation of cultured NPCs induced rapid phosphorylation of CPEB1, a hallmark of CPEB1-dependent translational control along with cyclin B1 polyadenylation and translation. EGF-induced activation of ERK1/2 and Aurora A kinase was responsible for CPEB1 phosphorylation. Pharmacological inhibition studies suggested that ERK1/2 is involved in the activation of Aurora A kinase and regulation of CPEB1 phosphorylation in cultured NPCs. Long-term incubation in EGF resulted in the down-regulation of CPEB1 expression, which further increased expression of cyclin B1 and cell cycle progression. When we down-regulated the expression of CPEB1 in NPCs by siRNA transfection, the proliferation of NPCs was increased. Increased NPCs proliferation by down-regulation of CPEB1 resulted in eventual up-regulation of neuronal differentiation with increase in both pre- and post-synaptic proteins. The results from the present study may suggest the importance of translational control in the regulation of neuronal development, an emerging concept in many neurodevelopmental and psychiatric disorders such as autism spectrum disorder.

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Acknowledgments

This work was supported by a grant of the Korean Health Technology R&D Project, Ministry of health & welfare, Republic of Korea (No. A120029), and the framework of international cooperation program (2012K2A1A2032549) through the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST).

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Authors and Affiliations

  1. Center for Neuroscience Research, SMART Institute of Advanced Biomedical Sciences, Konkuk University, Seoul, Korea

    Ki Chan Kim, Ji-Woon Kim, Chang Soon Choi, Seol-Heui Han & Chan Young Shin

  2. Department of Pharmacology, College of Pharmacy, Seoul National University, Seoul, Korea

    Ki Chan Kim

  3. Institute for Functional Genomics, School of Medicine, Konkuk University, Seoul, Korea

    Ji-Woon Kim, Chang Soon Choi & Chan Young Shin

  4. College of Pharmacy, Gyeongsang National University, **ju, Korea

    Sun Young Han

  5. Department of Pharmacy, Sahmyook University, Seoul, Korea

    Jae Hoon Cheong

  6. Department of Pharmacology, School of Medicine, Konkuk University, 1 Hwayang-Dong Kwang**-Gu, Seoul, 143-701, Korea

    Sung-Il Yang & Chan Young Shin

  7. Department of Neuropsychiatry, School of Medicine, Kyung Hee University, 1 Hoegi-Dong, Dong Dae Moon-Gu, Seoul, 130-702, Korea

    Geon Ho Bahn

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  1. Ki Chan Kim
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Correspondence to Geon Ho Bahn or Chan Young Shin.

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Ki Chan Kim and Ji-Woon Kim have contributed equally to this work.

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Kim, K.C., Kim, JW., Choi, C.S. et al. A Role of CPEB1 in the Modulation of Proliferation and Neuronal Maturation of Rat Primary Neural Progenitor Cells. Neurochem Res 38, 1960–1972 (2013). https://doi.org/10.1007/s11064-013-1102-4

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  • DOI: https://doi.org/10.1007/s11064-013-1102-4

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