TitleEvolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways.
Publication TypeJournal Article
Year of Publication2017
AuthorsSigg MAbedin, Menchen T, Lee C, Johnson J, Jungnickel MK, Choksi SP, Garcia G, Busengdal H, Dougherty GW, Pennekamp P, Werner C, Rentzsch F, Florman HM, Krogan N, Wallingford JB, Omran H, Reiter JF
JournalDev Cell
Date Published2017 12 18
KeywordsAdaptor Proteins, Signal Transducing, Animals, Calmodulin-Binding Proteins, Cell Culture Techniques, Choanoflagellata, Cilia, Hedgehog Proteins, Humans, Mice, Mutation, Organelles, Phylogeny, Proteomics, Receptors, G-Protein-Coupled, Sea Anemones, Sea Urchins, Signal Transduction, Transient Receptor Potential Channels, Xenopus laevis, Zebrafish

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.

Alternate JournalDev. Cell
PubMed ID29257953
PubMed Central IDPMC5752135
Grant ListR01 GM095941 / GM / NIGMS NIH HHS / United States
P30 DK098722 / DK / NIDDK NIH HHS / United States
R01 HL117164 / HL / NHLBI NIH HHS / United States
R01 HD046948 / HD / NICHD NIH HHS / United States
R01 AR054396 / AR / NIAMS NIH HHS / United States