Lee Seung-Hee, Shim Jaehoon, Cheong Ye-Hwang, Choi Sun-Lim, Jun Yong-Woo, Lee Sue-Hyun, Chae Yeon-Su, Han Jin-Hee, Lee Yong-Seok, Lee Jin-A, Lim Chae-Seok, Si Kausik, Kassabov Stefan, Antonov Igor, Kandel Eric R, Kaang Bong-Kiun, Jang Deok-Jin
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.
Mol Brain. 2016 Oct 22;9(1):91. doi: 10.1186/s13041-016-0271-x.
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.
海兔中，突触特异性的长期突触易化（LTF）需要两种药理学上不同类型的局部蛋白质合成：一种用于启动，另一种用于维持。ApCPEB是一种对雷帕霉素敏感的朊病毒样分子，它调节一种局部蛋白质合成形式，这种形式是维持LTF所特别需要的。然而，启动LTF所需的、对放线菌酮敏感的局部蛋白质合成的分子成分尚不清楚。在这里，我们鉴定出一种负责启动LTF的ApCPEB同源物。我们根据其哺乳动物CPEB4样同源物命名的ApCPEB4缺乏朊病毒样结构域，对5-羟色胺有反应，并以一种对放线菌酮敏感、对雷帕霉素不敏感且依赖蛋白激酶A的方式进行翻译（但不转录）。ApCPEB4与ApCPEB结合不同的靶RNA。敲低ApCPEB4会阻断LTF的诱导，而ApCPEB4的过表达会降低LTF形成的阈值。因此，我们的研究结果表明，两种不同形式的CPEB在LTF中发挥不同作用；ApCPEB是维持LTF所必需的，而缺乏朊病毒样结构域的ApCPEB4是启动LTF所必需的。
