Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, and Institute for Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.
Hum Mol Genet. 2011 Oct 15;20(R2):R149-57. doi: 10.1093/hmg/ddr354. Epub 2011 Aug 23.
Research of cilia has gained significant momentum in the last 15 years, as an increasing number of human genetic diseases were found to be caused by disruption of a protein that localizes to cilia. These ciliopathies are as diverse as the functions of the associated proteins, covering a spectrum of overlapping phenotypes that ranges from relatively mild characteristics in isolated tissues with a late onset, to severe defects of multiple tissues with an onset early in embryogenesis that is incompatible with life. As cilia harbour many receptors and components of key signaling cascades, such as Hedgehog, Wnt, Notch and Hippo signaling, disruption of ciliary function has severe consequences. Recent (affinity) proteomics studies have focused on the composition and dynamics of ciliary protein interaction networks. This has unveiled important knowledge about the highly ordered, interconnected but very dynamic nature of the cilium as a molecular machine. Disruption of the members of the same functional modules of this machine leads to similar phenotypes, and detailed analyses of the binding repertoire, the biochemical properties and the biological functions of these modules have yielded new ciliopathy genes as well as new insights into the pathogenic mechanisms underlying ciliopathies.
在过去的 15 年中，纤毛的研究取得了重大进展，因为越来越多的人类遗传疾病被发现是由于定位于纤毛的蛋白质的破坏。这些纤毛病与相关蛋白的功能一样多样化，涵盖了一系列重叠的表型，从在发病较晚的孤立组织中相对较轻的特征，到在胚胎发生早期发病且与生命不相容的多种组织的严重缺陷。由于纤毛包含许多受体和关键信号级联的组成部分，如 Hedgehog、Wnt、Notch 和 Hippo 信号，因此纤毛功能的破坏会产生严重的后果。最近（亲和）蛋白质组学研究集中在纤毛蛋白相互作用网络的组成和动态上。这揭示了关于纤毛作为一种分子机器的高度有序、相互关联但非常动态的性质的重要知识。同一功能模块的成员的破坏会导致类似的表型，对这些模块的结合谱、生化特性和生物学功能的详细分析产生了新的纤毛病基因，并深入了解了纤毛病的致病机制。
