Rayman Joseph B, Kandel Eric R
Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, New York 10032.
Cold Spring Harb Perspect Biol. 2017 May 1;9(5):a030718. doi: 10.1101/cshperspect.a030718.
Prions are self-propagating protein conformations that are traditionally regarded as agents of neurodegenerative disease in animals. However, it has become evident that prion-like aggregation of endogenous proteins can also occur under normal physiological conditions (e.g., during memory storage or activation of the immune response). In this review, we focus on the functional prion-related protein TIA-1, an RNA-binding protein that is involved in multiple aspects of RNA metabolism but is best understood in terms of its role in stress granule assembly during the cellular stress response. We propose that stress granule formation provides a useful conceptual framework with which to address the positive role of TIA-1 prion-like aggregation. Elucidating the function of TIA-1 prion-like aggregation will advance our understanding of how prion-based molecular switches are used in normal physiological settings.
朊病毒是自我传播的蛋白质构象，传统上被视为动物神经退行性疾病的病原体。然而，越来越明显的是，内源性蛋白质的朊病毒样聚集也可在正常生理条件下发生（例如，在记忆存储或免疫反应激活期间）。在本综述中，我们重点关注功能性朊病毒相关蛋白TIA-1，它是一种RNA结合蛋白，参与RNA代谢的多个方面，但就其在细胞应激反应期间应激颗粒组装中的作用而言，人们对它的了解最为深入。我们认为，应激颗粒的形成提供了一个有用的概念框架，用以探讨TIA-1朊病毒样聚集的积极作用。阐明TIA-1朊病毒样聚集的功能将增进我们对基于朊病毒的分子开关在正常生理环境中如何发挥作用的理解。
