Recent (affinity) proteomics studies have focused on thecomposition and dynamics of ciliary protein interactionnetworks. This has unveiled important knowledge aboutthe highly ordered, interconnected but very dynamicnature of the cilium as a molecular machine in the cell.Disruption of members of functional modules of thismachine leads to overlapping phenotypes. Detailed analysesof the binding repertoire, the biochemical propertiesand the biological functions of such modules have yieldedthe identification of new ciliopathy genes as well as newinsights into the pathogenic mechanisms underlying ciliopathies.To gain better insights into the molecular diseasemechanisms that underlie ciliopathies and to acquireknowledge about the general importance of the cilium forcellular homeostasis, we are conducting ciliary interactomestudies and will combine this information with subcellularlocalization data, and functional data derived from geneknockdown in ciliated cells or knockout/mutant vertebratemodels. This integrated dataset enables us to generatemodels of interacting functional modules associated withcell signalling cascades, developmental events or specificciliary functions such as intraflagellar transport. To date,we have performed affinity proteomics for the majority ofknown ciliopathy-associated proteins and many other ciliaryproteins. In addition, yeast two-hybrid experimentshave been performed to study the physical interactionbetween ciliary proteins in more detail. Our current datasetshows high interconnectivity between many of theciliopathy-associated proteins. These may be part of functionalciliary modules as many are associated with clinicallyoverlapping phenotypes. In addition, new membersof these modules are excellent novel candidate ciliopathyproteins.
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