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Scrutinizing ciliopathies by unraveling ciliary interaction networks.

Human Molecular Genetics 2011 October 16
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.

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