Structural basis of BBSome-mediated ciliary exit

项目总结 初级纤毛组织信号通路，如视觉、嗅觉和刺猬信号。正常运作 这些途径严重依赖于分子进出纤毛的运动，但我们的 对通过纤毛进行贩运的基本机制的了解仍然支离破碎。过去的工作 从实验室鉴定并鉴定了BBSome，这是一种蛋白质复合体，负责将信号受体运送出 纤毛和清除光感受器外段的不需要的蛋白质。BBSome与人类的相关性 健康和疾病的证据是一些BBSs功能障碍导致Bardet-Biedl综合征(BBS)，一种 遗传性疾病，以肥胖、视网膜退化、多指和肾脏畸形为特征。 这项提议的主要目标是确定分子齿轮和杠杆的结构和功能。 在BBSome内，可以选择性地从纤毛中去除蛋白质。拟议的研究将带来新的曙光。 关于纤毛贩运，并为今后的治疗干预奠定了基础。

PROJECT SUMMARY Primary cilia organize signaling pathways such as vision, olfaction and Hedgehog signaling. Proper functioning of these pathways is critically dependent on the movements of molecules into, inside and out of cilia, yet our understanding of the basic mechanisms governing trafficking through cilia remains fragmentary. Past work from the lab identified and characterized the BBSome, a protein complex that ferries signaling receptors out of cilia and clears photoreceptor outer segments of unwanted proteins. The relevance of the BBSome to human health and disease is evidence by the fact that BBSome dysfunction causes Bardet-Biedl Syndrome (BBS), a hereditary disease characterized by obesity, retinal degeneration, polydactyly and kidney malformations. The major goal of this proposal is to determine the structure and function of the molecular cogs and levers within the BBSome that enable selective removal of proteins from cilia. The proposed studies will cast new light on ciliary trafficking and lay the basis of future therapeutic interventions.