LZTFL1调控BBSome鞭毛内运输的分子机制研究

纤毛是存在于真核细胞表面，具有运动、感知和信号传导功能的细胞器。纤毛的感知和信号传导功能依赖于定位在纤毛膜上的信号蛋白。这些信号蛋白依赖由八种保守蛋白组成的多蛋白复合物BBSome，并以鞭毛内运输（intraflagellar transport，IFT）方式输入或输出纤毛。因此，BBSome在纤毛内缺失或定位异常均可导致纤毛内信号蛋白的异常缺失或累积，从而引发巴德-毕德氏综合症（Bardet-Biedl syndrome，BBS）。目前有研究表明，在哺乳动物细胞中，类亮氨酸拉链转录因子1（LZTFL1）缺失导致纤毛内BBSome累积而引发BBS，但是其背后详细的分子机制仍不清晰。因此，本项目将利用莱茵衣藻为模式生物，运用生物化学、遗传学和全内反射荧光成像技术等多种生物学手段研究LZTFL1调控BBSome鞭毛内运输的分子机制，从而有助于拓宽对BBS致病机理的理解。

Cilia are present on the surface of eukaryotic cells and have motility, sensory and signal transduction functions. The cilia’s capacity to sense and transduce extracellular signals depends on ciliary membrane proteins. These signaling proteins relied on BBSome, a multi protein complex composed of eight conserved proteins, enter or remove from cilia via intraflagellar transport (IFT) for maintaining their ciliary dynamics. Therefore, defects in BBSome assembly and ciliary distribution cause loss or abnormal accumulation of ciliary signaling proteins, eventually resulting in Bardet-Biedl syndrome (BBS). Nowadays, studies show that lack of leucine zipper transcription factor-like 1 (LZTFL1) results in the accumulation of BBSome, eventually leading to BBS, while the mechanism underlying this process remains largely elusive. Therefore, this project will study the molecular mechanism of LZTFL1 regulating the BBSome dynamics in cilia by using biochemical, genetic and total internal reflection fluorescence imaging assays on Chlamydomonas reinhardtii, which will help to broaden the understanding of the pathogenic mechanism of BBS.