Veland Iben R, Awan Aashir, Pedersen Lotte B, Yoder Bradley K, Christensen Søren T
Department of Biology, Section of Cell and Developmental Biology, University of Copenhagen, Copenhagen, Denmark.
Nephron Physiol. 2009;111(3):p39-53. doi: 10.1159/000208212. Epub 2009 Mar 10.
Although first described as early as 1898 and long considered a vestigial organelle of little functional importance, the primary cilium has become one of the hottest research topics in modern cell biology and physiology. Primary cilia are nonmotile sensory organelles present in a single copy on the surface of most growth-arrested or differentiated mammalian cells, and defects in their assembly or function are tightly coupled to many developmental defects, diseases and disorders. In normal tissues, the primary cilium coordinates a series of signal transduction pathways, including Hedgehog, Wnt, PDGFRalpha and integrin signaling. In the kidney, the primary cilium may function as a mechano-, chemo- and osmosensing unit that probes the extracellular environment and transmits signals to the cell via, e.g., polycystins, which depend on ciliary localization for appropriate function. Indeed, hypomorphic mutations in the mouse ift88 (previously called Tg737) gene, which encodes a ciliogenic intraflagellar transport protein, result in malformation of primary cilia, and in the collecting ducts of kidney tubules this is accompanied by development of autosomal recessive polycystic kidney disease (PKD). While PKD was one of the first diseases to be linked to dysfunctional primary cilia, defects in this organelle have subsequently been associated with many other phenotypes, including cancer, obesity, diabetes as well as a number of developmental defects. Collectively, these disorders of the cilium are now referred to as the ciliopathies. In this review, we provide a brief overview of the structure and function of primary cilia and some of their roles in coordinating signal transduction pathways in mammalian development, health and disease.
尽管早在1898年就首次被描述，并且长期以来一直被认为是功能不太重要的退化细胞器，但初级纤毛已成为现代细胞生物学和生理学中最热门的研究课题之一。初级纤毛是大多数生长停滞或分化的哺乳动物细胞表面单个存在的非运动性感觉细胞器，其组装或功能缺陷与许多发育缺陷、疾病和病症紧密相关。在正常组织中，初级纤毛协调一系列信号转导途径，包括Hedgehog、Wnt、PDGFRα和整合素信号传导。在肾脏中，初级纤毛可能作为机械、化学和渗透压传感单元，探测细胞外环境并通过例如多囊蛋白将信号传递给细胞，多囊蛋白的正常功能依赖于其在纤毛上的定位。实际上，编码纤毛生成性鞭毛内运输蛋白的小鼠ift88（以前称为Tg737）基因的亚效突变会导致初级纤毛畸形，在肾小管集合管中，这会伴有常染色体隐性多囊肾病（PKD）的发展。虽然PKD是最早与功能失调的初级纤毛相关的疾病之一，但随后这种细胞器的缺陷还与许多其他表型有关，包括癌症、肥胖、糖尿病以及一些发育缺陷。总的来说，这些纤毛疾病现在被称为纤毛病。在这篇综述中，我们简要概述了初级纤毛的结构和功能，以及它们在协调哺乳动物发育、健康和疾病中的信号转导途径中的一些作用。
