Striebel James F, Carroll James A, Race Brent, Leung Jacqueline M, Schwartz Cindi, Reese Emily D, Bowes Rickman Catherine, Chesebro Bruce, Klingeborn Mikael
Laboratory of Neurological Infections and Immunity, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
iScience. 2024 Sep 13;27(10):110954. doi: 10.1016/j.isci.2024.110954. eCollection 2024 Oct 18.
The prion protein, PrP, is well known as an essential susceptibility factor for neurodegenerative prion diseases, yet its function in normal, healthy cells remains uncertain. A role in synaptic function has been proposed for PrP, supported by its cell surface expression in neurons and glia. Here, in mouse retina, we localized PrP to the junctions between photoreceptors and bipolar cells using synaptic proteins EAAT5, CtBP2, and PSD-95. PrP localized most densely with bipolar cell dendrites synapsing with cone photoreceptors. In two coisogenic mouse strains, deletion of the gene encoding PrP, , significantly altered the scotopic and/or photopic electroretinographic (ERG) responses of photoreceptors and bipolar cells. Cone-dominant pathways showed the most significant ERG changes. Retinal thickness, quantitated by high-resolution optical coherence tomography (OCT), and ribbon synapse morphology were not altered upon deletion of PrP, suggesting that the ERG changes were driven by functional rather than structural alterations.
朊病毒蛋白（PrP）作为神经退行性朊病毒疾病的一个重要易感因素而广为人知，然而其在正常健康细胞中的功能仍不明确。鉴于PrP在神经元和神经胶质细胞的细胞表面表达，有人提出它在突触功能中发挥作用。在此，我们利用突触蛋白EAAT5、CtBP2和PSD-95，在小鼠视网膜中，将PrP定位到光感受器与双极细胞之间的连接处。PrP最密集地定位于与视锥光感受器形成突触的双极细胞树突上。在两个同基因小鼠品系中，编码PrP的基因缺失显著改变了光感受器和双极细胞的暗视和/或明视视网膜电图（ERG）反应。以视锥为主的通路显示出最显著的ERG变化。通过高分辨率光学相干断层扫描（OCT）定量的视网膜厚度以及带状突触形态在PrP基因缺失后并未改变，这表明ERG变化是由功能改变而非结构改变所驱动。
