Cell Reports: 视觉逃避行为可塑性需要CPEB的快速合成

2014-05-28 18:01:57 admin
这篇发表在CELL REPORTS上的论文由杭州师范大学和SCRIPPS研究所共同完成,论文第一作者为杭州师范大学器官与发育重点实验室沈万华教授。神经可塑性需要蛋白质的合成,但如何鉴别可塑性刺激产生的新合成蛋白质仍不清楚。这篇论文使用了在体的生物正交非经典氨基酸标记( BONCAT )与甲硫氨酸类似物(azidohomoalanine,AHA)结合多维蛋白质鉴定技术( MudPIT )来标识24小时候内新合成的蛋白质。实验结果表明,视觉诱导的视觉回避行为具有可塑性,这个过程需要NMDA,钙通透的AMPA受体和 αCaMKII 参与的快速蛋白质合成。用免疫印迹结合BONCAT实验证实,包括αCaMKII , MEK1 ,GAD65的新蛋白合成是必需的,并在爪蟾视顶盖神经环路中参与了可塑性调节的CPEB快速合成。这篇论文系统的阐述了一个新蛋白质合成依赖的行为可塑性信号转导途径,为筛选经验依赖的新蛋白提供了科学方向。
Cell Rep. 2014 Feb 27;6(4):737-47.

Acute synthesis of CPEB is required for plasticity of visual avoidance behavior in Xenopus.

Shen W, Liu HH, Schiapparelli L, McClatchy D, He HY, Yates JR 3rd, Cline HT


Neural plasticity requires protein synthesis, but the identity of newly synthesized proteins generated in response to plasticity-inducing stimuli remains unclear. We used in vivo bio-orthogonal noncanonical amino acid tagging (BONCAT) with the methionine analog azidohomoalanine (AHA) combined with the multidimensional protein identification technique (MudPIT) to identify proteins that are synthesized in the tadpole brain over 24 hr. We induced conditioning-dependent plasticity of visual avoidance behavior, which required N-methyl-D-aspartate (NMDA) and Ca(2+)-permeable α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, αCaMKII, and rapid protein synthesis. Combining BONCAT with western blots revealed that proteins including αCaMKII, MEK1, CPEB, and GAD65 are synthesized during conditioning. Acute synthesis of CPEB during conditioning is required for behavioral plasticity as well as conditioning-induced synaptic and structural plasticity in the tectal circuit. We outline a signaling pathway that regulates protein-synthesis-dependent behavioral plasticity in intact animals, identify newly synthesized proteins induced by visual experience, and demonstrate a requirement for acute synthesis of CPEB in plasticity.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.