Cai Xin, Chen Zhijian J
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Trends Immunol. 2014 Dec;35(12):622-630. doi: 10.1016/j.it.2014.10.003. Epub 2014 Nov 12.
The innate immune system uses pattern recognition receptors such as RIG-I and NLRP3 to sense pathogen invasion and other danger signals. Activation of these receptors induces robust signal transduction cascades that trigger the production of cytokines important for host protection. MAVS and ASC are essential adaptor proteins downstream of RIG-I and NLRP3, respectively, and both contain N-terminal domains belonging to the death domain superfamily. Recent studies suggest that both MAVS and ASC form functional prion-like fibers through their respective death domains to propagate downstream signaling. Here, we review these findings, and in this context discuss the emerging concept of prion-like polymerization in signal transduction. We further examine the potential benefits of this signaling strategy, including signal amplification, host evolutionary advantage, and molecular memory.
先天性免疫系统利用RIG-I和NLRP3等模式识别受体来感知病原体入侵和其他危险信号。这些受体的激活会引发强大的信号转导级联反应，从而触发对宿主保护至关重要的细胞因子的产生。MAVS和ASC分别是RIG-I和NLRP3下游的重要衔接蛋白，两者都含有属于死亡结构域超家族的N端结构域。最近的研究表明，MAVS和ASC都通过各自的死亡结构域形成功能性的朊病毒样纤维，以传播下游信号。在此，我们回顾这些发现，并在此背景下讨论信号转导中朊病毒样聚合这一新兴概念。我们进一步研究了这种信号传导策略的潜在益处，包括信号放大、宿主进化优势和分子记忆。
