Bandura Julia, Chan Calvin, Sun Hong-Shuo, Wheeler Aaron R, Feng Zhong-Ping
Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
J Proteome Res. 2025 Jan 3;24(1):27-45. doi: 10.1021/acs.jproteome.4c00055. Epub 2024 Dec 10.
Long-term memory (LTM) formation relies on protein synthesis; however, the full complement of proteins crucial to LTM formation remains unknown in any system. Using an aversive operant conditioning model of aerial respiratory behavior in the pond snail mollusk, (), we conducted a transcriptome-guided proteomic analysis on the central nervous system (CNS) of LTM, no LTM, and control animals. We identified 366 differentially expressed proteins linked to LTM formation, with 88 upregulated and 36 downregulated in LTM compared to both no LTM and controls. Functional annotation highlighted the importance of balancing protein synthesis and degradation for LTM, as indicated by the upregulation of proteins involved in proteasome activity and translation initiation, including EIF2D, mRNA levels of which were confirmed to be upregulated by conditioning and implicated nuclear factor Y as a potential regulator of LTM-related transcription in this model. This study represents the first transcriptome-guided proteomic analysis of LTM formation ability in this model and lays the groundwork for discovering orthologous proteins critical to LTM in mammals.
长期记忆（LTM）的形成依赖于蛋白质合成；然而，在任何系统中，对LTM形成至关重要的完整蛋白质组仍然未知。我们利用池塘蜗牛软体动物空中呼吸行为的厌恶操作性条件反射模型，对形成LTM、未形成LTM和对照动物的中枢神经系统（CNS）进行了转录组引导的蛋白质组分析。我们鉴定出366种与LTM形成相关的差异表达蛋白，与未形成LTM和对照动物相比，LTM中有88种上调，36种下调。功能注释突出了平衡蛋白质合成和降解对LTM的重要性，这表现为参与蛋白酶体活性和翻译起始的蛋白质上调，包括EIF2D，其mRNA水平经条件作用确认上调，并且在该模型中暗示核因子Y是LTM相关转录的潜在调节因子。本研究代表了在该模型中首次对LTM形成能力进行转录组引导的蛋白质组分析，并为发现哺乳动物中对LTM至关重要的直系同源蛋白奠定了基础。
