Children's Hospital Boston, 61 Binney Street, Enders 730.2, Boston, MA 02115, USA.
Front Biosci (Landmark Ed). 2011 Jun 1;16(6):2060-8. doi: 10.2741/3839.
While initial studies of Toll-like Receptor (TLR) signaling mainly focused on genetic analysis of signal transduction, recent work has highlighted the importance of understanding the basic cell biology underlying receptor function. Nowhere is this issue more important than in the study of the nucleic acid-sensing TLRs. These receptors face the unique challenge of distinguishing microbial nucleic acids from similar host-derived molecules. The physiological cost of not making this distinction can be readily observed in studies of autoimmunity, a cause of which is often the inappropriate detection of self nucleic acids. In this review, we highlight recent research that has revealed myriad ways in which mammalian cells control the function of nucleic acid-sensing TLRs. A theme is now emerging whereby these receptors are subject to sequential regulatory mechanisms that control protein transport to their sites of signal transduction, as well as their access microbial nucleic acids.
虽然 Toll 样受体（TLR）信号的初始研究主要集中在信号转导的遗传分析上，但最近的工作强调了理解受体功能基础细胞生物学的重要性。在核酸感应 TLR 的研究中，这个问题尤为重要。这些受体面临着从类似的宿主衍生分子中区分微生物核酸的独特挑战。在自身免疫的研究中，不进行这种区分的生理代价是显而易见的，自身核酸的不当检测常常是自身免疫的一个原因。在这篇综述中，我们强调了最近的研究揭示了哺乳动物细胞控制核酸感应 TLR 功能的无数种方式。一个主题正在浮现，即这些受体受到一系列调节机制的控制，这些机制控制着蛋白质向信号转导部位的运输，以及它们对微生物核酸的访问。
