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Publication

Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways.

Developmental cell | 2017

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.

Pubmed ID: 29257953 RIS Download

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Associated grants

Agency: NIGMS NIH HHS, United States
Id: R01 GM095941
Agency: NICHD NIH HHS, United States
Id: R01 HD085901
Agency: NIDDK NIH HHS, United States
Id: P30 DK098722
Agency: NHLBI NIH HHS, United States
Id: R01 HL117164
Agency: NICHD NIH HHS, United States
Id: R01 HD046948
Agency: NIDDK NIH HHS, United States
Id: R01 DK106404
Agency: NIAMS NIH HHS, United States
Id: R01 AR054396

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GraphPad Prism (tool)

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RRID:SCR_002344

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