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Publication : Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways.

First Author  Sigg MA Year  2017
Journal  Dev Cell Volume  43
Issue  6 Pages  744-762.e11
PubMed ID  29257953 Mgi Jnum  J:253966
Mgi Id  MGI:6110984 Doi  10.1016/j.devcel.2017.11.014
Citation  Sigg MA, et al. (2017) Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways. Dev Cell 43(6):744-762.e11
abstractText  Cilia are organelles specialized for movement and signaling. To infer when during evolution signaling pathways became associated with cilia, we characterized the proteomes of cilia from sea urchins, sea anemones, and choanoflagellates. We identified 437 high-confidence ciliary candidate proteins conserved in mammals and discovered that Hedgehog and G-protein-coupled receptor pathways were linked to cilia before the origin of bilateria and transient receptor potential (TRP) channels before the origin of animals. We demonstrated that candidates not previously implicated in ciliary biology localized to cilia and further investigated ENKUR, a TRP channel-interacting protein identified in the cilia of all three organisms. ENKUR localizes to motile cilia and is required for patterning the left-right axis in vertebrates. Moreover, mutation of ENKUR causes situs inversus in humans. Thus, proteomic profiling of cilia from diverse eukaryotes defines a conserved ciliary proteome, reveals ancient connections to signaling, and uncovers a ciliary protein that underlies development and human disease.
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