title: ApCPEB4, a non-prion domain containing homolog of ApCPEB, is involved in the initiation of long-term facilitation.
abstract: Two pharmacologically distinct types of local protein synthesis are required for synapse- specific long-term synaptic facilitation (LTF) in Aplysia: one for initiation and the other for maintenance. ApCPEB, a rapamycin sensitive prion-like molecule regulates a form of local protein synthesis that is specifically required for the maintenance of the LTF. However, the molecular component of the local protein synthesis that is required for the initiation of LTF and that is sensitive to emetine is not known. Here, we identify a homolog of ApCPEB responsible for the initiation of LTF. ApCPEB4 which we have named after its mammalian CPEB4-like homolog lacks a prion-like domain, is responsive to 5-hydroxytryptamine, and is translated (but not transcribed) in an emetine-sensitive, rapamycin-insensitive, and PKA-dependent manner. The ApCPEB4 binds to different target RNAs than does ApCPEB. Knock-down of ApCPEB4 blocked the induction of LTF, whereas overexpression of ApCPEB4 reduces the threshold of the formation of LTF. Thus, our findings suggest that the two different forms of CPEBs play distinct roles in LTF; ApCPEB is required for maintenance of LTF, whereas the ApCPEB4, which lacks a prion-like domain, is required for the initiation of LTF.
authors: Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1 Gwanangno, Gwanak-gu, Seoul, 08826, South Korea.|Department of Biological Sciences, KAIST, Daejeon, 34141, South Korea.
authors: Seung-Hee
authors: SH
authors: Lee
authors: Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1 Gwanangno, Gwanak-gu, Seoul, 08826, South Korea.
authors: Jaehoon
authors: J
authors: Shim
authors: Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1 Gwanangno, Gwanak-gu, Seoul, 08826, South Korea.
authors: Ye-Hwang
authors: YH
authors: Cheong
authors: Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1 Gwanangno, Gwanak-gu, Seoul, 08826, South Korea.
authors: Sun-Lim
authors: SL
authors: Choi
authors: Department of Ecological Science, College of Ecology and Environment, Kyungpook National University, 2559, Gyeongsang-daero, Sangjusi, Gyeongsangbuk-do, 37224, South Korea.
authors: Yong-Woo
authors: YW
authors: Jun
authors: Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1 Gwanangno, Gwanak-gu, Seoul, 08826, South Korea.|Department of Bio and Brain Engineering, KAIST, Daejeon, 34141, South Korea.
authors: Sue-Hyun
authors: SH
authors: Lee
authors: Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1 Gwanangno, Gwanak-gu, Seoul, 08826, South Korea.
authors: Yeon-Su
authors: YS
authors: Chae
authors: Department of Biological Sciences, KAIST, Daejeon, 34141, South Korea.
authors: Jin-Hee
authors: JH
authors: Han
authors: Department of Physiology, College of Medicine, Seoul National University, Seoul, 03080, South Korea.
authors: Yong-Seok
authors: YS
authors: Lee
authors: Department of Biotechnology and Biological Science, College of Life Science and Nano Technology, Hannam University, Daejeon, 34054, South Korea.
authors: Jin-A
authors: JA
authors: Lee
authors: Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1 Gwanangno, Gwanak-gu, Seoul, 08826, South Korea.
authors: Chae-Seok
authors: CS
authors: Lim
authors: Stowers Institute for Medical Research, Kansas City, MO, 64110, USA.
authors: Kausik
authors: K
authors: Si
authors: Howard Hughes Medical Institute, 1051 Riverside Drive, New York, NY, 10032, USA.
authors: Stefan
authors: S
authors: Kassabov
authors: Howard Hughes Medical Institute, 1051 Riverside Drive, New York, NY, 10032, USA.
authors: Igor
authors: I
authors: Antonov
authors: Howard Hughes Medical Institute, 1051 Riverside Drive, New York, NY, 10032, USA.|Department of Neuroscience, New York State Psychiatric Institute, Kavli Institute for Brain Sciences, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA.
authors: Eric R
authors: ER
authors: Kandel
authors: Department of Biological Sciences, College of Natural Sciences, Seoul National University, 1 Gwanangno, Gwanak-gu, Seoul, 08826, South Korea. kaang@snu.ac.kr.
authors: Bong-Kiun
authors: BK
authors: Kaang
authors: Department of Ecological Science, College of Ecology and Environment, Kyungpook National University, 2559, Gyeongsang-daero, Sangjusi, Gyeongsangbuk-do, 37224, South Korea. jangdj@knu.ac.kr.
authors: Deok-Jin
authors: DJ
authors: Jang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D002490:Central Nervous System / Q000502:physiology; D003001:Cloning, Molecular; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology*; D016501:Neurites / Q000378:metabolism; D010766:Phosphorylation; D011328:Prions / Q000737:chemistry*; D011485:Protein Binding; D000072417:Protein Domains; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011328:Prions; D016601:RNA-Binding Proteins; D012701:Serotonin; D012313:RNA; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Aplysia; CPEB; CPEB4; Long-term facilitation