细胞纤毛在信号转导与器官发育中的作用与机制

Cilia Function in Cell Signaling and Organ Development

纤毛(cilia)是细胞表面的突起状细胞器,几乎存在于所有细胞表面,且广泛分布于组织和器官的上皮.纤毛由外部的纤毛膜和内部的轴丝组成,结构在进化上十分保守.根据微管组成和排列方式的不同,纤毛可分为9+2型运动纤毛与9+0型基本纤毛或非运动纤毛.作为一种特殊的感受器,纤毛通过影响细胞信号通路参与胚胎形成、心脏等内脏器官发育及人体重要生理活动.本课题组在国际上首次把前列腺素信号通路与纤毛生长及心脏发育相联系.研究发现,ABCC4/LKT前列腺素转运蛋白从细胞内运输前列腺素E2(PGE2)至细胞外,并通过结合位于纤毛膜上的G蛋白偶联受体EP4影响细胞内c AMP浓度,调节纤毛内运输蛋白的正向速率,进而调控纤毛生长与心脏等器官的左右不对称性发育.纤毛生长或功能缺陷会引发先天性心脏病、多囊肾、视网膜变性等多种疾病.本文主要介绍纤毛参与调控细胞内信号转导与器官发育及相关纤毛疾病.

Cilia are extracellular organelles that protrude from the cell surface and are present in the epithelial cells lining every organ. The cilium structure is conserved, containing a ciliary membrane and microtubule-based axoneme. There are two types of cilia, including 9＋2 motile cilia and 9＋0 primary cilia. Cilia play important roles in embryogenesis, heart and other visceral organ development, and human physiological and pathological processes. Our studies showed that prostaglandin signaling plays a role in ciliogenesis and heart development. After being exported from cells through LKT/ABCC4 transporters, prostaglandin E2 upregulates intracellular c AMP synthesis through the G-protein-coupled receptor EP4 on the cilium. This increases the anterograde velocity of intraflagellar transport and regulates the left-right asymmetry of heart and other organs. Cilia defects cause a variety of human diseases including congenital heart disease, polycystic kidney disease, and retinal degeneration. This review outlines the various roles of cilia in signal transduction, organ development, and human ciliopathies.