Tsui C C, Copeland N G, Gilbert D J, Jenkins N A, Barnes C, Worley P F
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Neurosci. 1996 Apr 15;16(8):2463-78. doi: 10.1523/JNEUROSCI.16-08-02463.1996.
Stimulus-linked RNA and protein synthesis is required for establishment of long-term neuroplasticity. To identify molecular mechanisms underlying long-term neuroplasticity, we have used differential cDNA techniques to clone a novel immediate-early gene (IEG) that is rapidly induced in neurons of the hippocampus and cortex by physiological synaptic activity. Analysis of the deduced amino acid sequence indicates homology to members of the pentraxin family of secreted lectins that include C-reactive protein and serum amyloid P component. Regions of homology include an 8 amino acid "pentraxin signature" sequence and a characteristic pentraxin calcium-binding domain. We have termed this gene and the encoded protein Narp (from neuronal activity-regulated pentraxin). Biochemical analyses confirm the presence of a functional signal sequence, and Narp is secreted by transfected COS-1 cells in culture. Additionally, Narp binds to agar matrix in a calcium-dependent manner consistent with the lectin properties of the pentraxin family. When cocultured with Narp-secreting COS-1 cells, neurons of cortical explants exhibit enhanced growth of neuronal dendritic processes. Neurite outgrowth-promoting activity is also observed using partially purified Narp and can be specifically immunodepleted, demonstrating that Narp is the active principle. Narp is fully active at a concentration of approximately 40 ng/ml, indicating a potency similar to known peptide growth factors. Because Narp is rapidly regulated by neuronal activity, its lectin and growth-promoting activities are likely to play role in the modification of cellular properties that underlie long-term plasticity.
长期神经可塑性的建立需要与刺激相关的RNA和蛋白质合成。为了确定长期神经可塑性背后的分子机制，我们使用差异cDNA技术克隆了一个新的即早基因（IEG），该基因在海马体和皮质的神经元中被生理突触活动快速诱导。对推导的氨基酸序列的分析表明，它与包括C反应蛋白和血清淀粉样蛋白P成分在内的分泌型凝集素的五聚体蛋白家族成员具有同源性。同源区域包括一个8个氨基酸的“五聚体蛋白特征”序列和一个特征性的五聚体蛋白钙结合结构域。我们将这个基因及其编码的蛋白命名为Narp（源自神经元活性调节的五聚体蛋白）。生化分析证实存在功能性信号序列，并且Narp在培养的转染COS-1细胞中分泌。此外，Narp以与五聚体蛋白家族的凝集素特性一致的钙依赖性方式结合琼脂基质。当与分泌Narp的COS-1细胞共培养时，皮质外植体的神经元表现出神经元树突状突起的生长增强。使用部分纯化的Narp也观察到神经突生长促进活性，并且可以被特异性免疫去除，这表明Narp是活性成分。Narp在浓度约为40 ng/ml时具有完全活性，表明其效力与已知的肽生长因子相似。由于Narp受神经元活动快速调节，其凝集素和生长促进活性可能在长期可塑性基础的细胞特性修饰中起作用。
