A novel cysteine-rich neurotrophic factor in Aplysia facilitates growth, MAPK activation, and long-term synaptic facilitation.-猫眼课题宝

DOI：

10.1101/lm.033662.113

发表时间：

2014-04-01

期刊：

Learning & memory (Cold Spring Harbor, N.Y.)

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Pu L;Kopec AM;Boyle HD;Carew TJ

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3966541/?report=classic

神经营养因子在神经细胞的存活、生长和分化等发育过程中起着至关重要的作用，也参与了促进学习和记忆的成人突触可塑性。我们之前对澳大利亚神经营养因子和记忆形成的研究表明，TrkB配体是MAPK激活、长期突触促进（LTF）和长期记忆（LTM）致敏所需的。这些研究表明，澳大利亚的神经营养因子样分子可以作为功能保守的TrkB信号通路的关键元件。本文作者克隆并鉴定了一种新的神经营养因子——富半胱氨酸神经营养因子（apCRNF），它具有与哺乳动物神经营养因子相同的经典结构和功能特征。我们发现apCRNF(1)在中枢神经系统中高度富集，(2)增强神经突伸长和分支，(3)与哺乳动物TrkB和p75NTR相互作用，(4)以活性依赖的方式从澳大利亚中枢神经系统释放，(5)在敏化刺激下以酪氨酸激酶依赖的方式促进MAPK激活，(6)促进LTF的诱导。这些结果表明apCRNF是一种天然的神经营养因子，可以参与记忆形成的分子和突触机制。

Neurotrophins are critically involved in developmental processes such as neuronal cell survival, growth, and differentiation, as well as in adult synaptic plasticity contributing to learning and memory. Our previous studies examining neurotrophins and memory formation in Aplysia showed that a TrkB ligand is required for MAPK activation, long-term synaptic facilitation (LTF), and long-term memory (LTM) for sensitization. These studies indicate that neurotrophin-like molecules in Aplysia can act as key elements in a functionally conserved TrkB signaling pathway. Here we report that we have cloned and characterized a novel neurotrophic factor, Aplysia cysteine-rich neurotrophic factor (apCRNF), which shares classical structural and functional characteristics with mammalian neurotrophins. We show that apCRNF (1) is highly enriched in the CNS, (2) enhances neurite elongation and branching, (3) interacts with mammalian TrkB and p75NTR, (4) is released from Aplysia CNS in an activity-dependent fashion, (5) facilitates MAPK activation in a tyrosine kinase dependent manner in response to sensitizing stimuli, and (6) facilitates the induction of LTF. These results show that apCRNF is a native neurotrophic factor in Aplysia that can engage the molecular and synaptic mechanisms underlying memory formation.