ApCPEB4, a non-prion domain containing homolog of ApCPEB, is involved in the initiation of long-term facilitation.

Seung-Hee Lee,Jin-A Lee,Jaehoon Shim,Chae-Seok Lim,Bong-Kiun Kaang,Yeon-Su Chae,Sue-Hyun Lee,Sun-Lim Choi,Ye-Hwang Cheong,Eric R Kandel,Igor Antonov,Yong-Seok Lee,Yong-Woo Jun,Stefan Kassabov,Jin-Hee Han,Deok-Jin Jang,Kausik Si

doi:10.1186/s13041-016-0271-x

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-016-0271-x) contains supplementary material, which is available to authorized users.

Highlights

Unlike short-term memory, long-term memory requires new protein synthesis for its formation [1,2,3,4,5,6,7]
The amino acid sequences of the Aplysia CPEB4 (ApCPEB4) RRM domain are 83.0 % identical to mouse CPEB2, 82.0 % to mouse CPEB3, 80.7 % to mouse CPEB4, 77.4 % to Orb2, 34.4 % to mouse CPEB1, 32.7 to Orb1 and 31.0 % to Aplysia CPEB (ApCPEB), respectively. These analyses suggest that ApCPEB4 is homologous to the members of the mammalian CPEB2-4 family
Whereas ApCPEB is critical for maintenance, the translational increase of ApCPEB4 was critical for the formation of long-term synaptic facilitation (LTF)

Summary

Introduction

Unlike short-term memory, long-term memory requires new protein synthesis for its formation [1,2,3,4,5,6,7]. The second form of translation is responsible for local protein synthesis, which is important for both the initiation and the maintenance of long-term memory. The cytoplasmic polyadenylation element binding protein (CPEB) has been identified as one key regulator of the local protein synthesis in Aplysia [6]. The binding of CPEB to mRNAs regulates the translation of target mRNAs by regulating their polyadenylation [11,12,13,14]. ApCPEB has a prion-like domain that is important for the ability of ApCPEB to form aggregates that are self-sustaining and can maintain the increased level of ApCPEB proteins in the terminals that is critical for maintaining long-term facilitation (LTF) in Aplysia sensory-motor neuron synapse [15,16,17].

Methods

Results

Conclusion