Cellular and molecular aspects of Toll-like receptor signal transduction.

项目摘要 建立有效免疫反应的能力对人类健康至关重要。Toll样受体（TLR） 是在吞噬细胞和其他细胞上表达的跨膜蛋白，作为微生物的传感器， 感染最近的研究强调了TLR在先天性和适应性免疫中的重要性， TLR信号传导缺陷的小鼠在控制细菌和病毒感染方面存在缺陷。尽管 确定TLR信号传导所需的几个基因，清楚地了解TLR信号传导如何复合 是如何组装的，如何组装是缺乏的。该提案将研究蜂窝和 TLR信号转导的分子方面。我们将重点关注四个基本特征的表征 TLR衔接蛋白在其定位和募集到携带活化TLR的膜方面的差异。 将鉴定并突变介导衔接子定位和募集至TLR的顺式作用结构域 作为解决TLR信号传导中衔接子定位的功能意义的手段。反式 调节适配器定位的因素将被确定，特别关注运输调节 磷酸肌醇。该项目的成功完成将使人们对蜂窝通信技术有重要的了解。 TLR信号转导的控制，从而免疫机制。

Project Summary The ability to mount an effective immune response is critical for human health. Toll-like receptors (TLRs) are transmembrane proteins expressed on phagocytes and other cells that act as sensors of microbial infection. Recent studies have underscored the importance of TLRs in innate and adaptive immunity as mice deficient in TLR signaling have defects in controlling bacterial and viral infections. Despite the indentification of several genes required for TLR signaling, a clear picture of how TLR signaling complexes are assembled and how assembly is regulated is lacking. This proposal will investigate cellular and molecular aspects of TLR signal transduction. We will focus on the characterization of the four essential TLR adaptor proteins in terms of their localization and recruitment to membranes bearing activated TLRs. Cis-acting domains that mediate adaptor localization and recruitment to TLRs will be identified and mutated as a means of addressing the functional significance of adaptor localization in TLR signaling. Trans-acting factors that regulate adaptor localization will be identified with a particular focus on the transport regulation by phosphoinositides. The successful completion of this project will yeild important insight into cellular control of TLR signal transduction and thus, mechanisms of immunity.