Department of Pharmacology and Chemical Biology, Rollins Research Center , Emory University School of Medicine , Atlanta , Georgia 30322 , United States.
Department of Biochemistry , Emory University School of Medicine , Atlanta , Georgia 30322 , United States.
J Proteome Res. 2019 Jun 7;18(6):2571-2584. doi: 10.1021/acs.jproteome.9b00103. Epub 2019 May 14.
The hippocampus is well established as an essential brain center for learning and memory. Within the hippocampus, recent studies show that area CA2 is important for social memory and is an anomaly compared to its better-understood neighboring region, CA1. Unlike CA1, CA2 displays a lack of typical synaptic plasticity, enhanced calcium buffering and extrusion, and resilience to cell death following injury. Although recent studies have identified multiple molecular markers of area CA2, the proteins that mediate the unique physiology, signaling, and resilience of this region are unknown. Using a transgenic GFP-reporter mouse line that expresses eGFP in CA2, we were able to perform targeted dissections of area CA2 and CA1 for proteomic analysis. We identified over 100 proteins with robustly enriched expression in area CA2 compared to CA1. Many of these proteins, including RGS14 and NECAB2, have already been shown to be enriched in CA2 and important for its function, while many more merit further study in the context of enhanced expression in this enigmatic brain region. Furthermore, we performed a comprehensive analysis of the entire data set (>2300 proteins) using a weighted protein co-expression network analysis. This identified eight distinct co-expressed patterns of protein co-enrichment associated with increased expression in area CA2 tissue (compared to CA1). The novel data set we present here reveals a specific CA2 hippocampal proteome, laying the groundwork for future studies and a deeper understanding of area CA2 and the proteins mediating its unique physiology and signaling.
海马体是学习和记忆的重要脑区，这一点已得到充分证实。在海马体中，最近的研究表明 CA2 区对于社会记忆很重要，与相邻的 CA1 区相比，它是一个异类。与 CA1 不同，CA2 区表现出缺乏典型的突触可塑性、增强的钙缓冲和排出，以及受伤后细胞死亡的抵抗力。尽管最近的研究已经确定了 CA2 区的多个分子标记物，但介导该区域独特生理学、信号传递和恢复能力的蛋白质仍然未知。使用一种在 CA2 中表达 GFP 的转基因 GFP 报告鼠系，我们能够对 CA2 和 CA1 区进行靶向解剖，用于蛋白质组学分析。与 CA1 相比，我们在 CA2 区中鉴定出 100 多种表达丰富的蛋白质。其中许多蛋白质，包括 RGS14 和 NECAB2，已经被证明在 CA2 中丰富存在并对其功能很重要，而更多的蛋白质在这个神秘的脑区表达增强的背景下值得进一步研究。此外，我们使用加权蛋白质共表达网络分析对整个数据集（超过 2300 种蛋白质）进行了全面分析。这确定了与 CA2 组织中表达增加（与 CA1 相比）相关的 8 种不同的蛋白质共富集共表达模式。我们在这里呈现的新数据集揭示了一个特定的 CA2 海马体蛋白质组，为未来的研究以及对 CA2 区及其介导的独特生理学和信号传递的蛋白质的更深入理解奠定了基础。
