Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways

Publication date: 18 December 2017
Source:Developmental Cell, Volume 43, Issue 6
Author(s): Monika Abedin Sigg, Tabea Menchen, Chanjae Lee, Jeffery Johnson, Melissa K. Jungnickel, Semil P. Choksi, Galo Garcia, Henriette Busengdal, Gerard W. Dougherty, Petra Pennekamp, Claudius Werner, Fabian Rentzsch, Harvey M. Florman, Nevan Krogan, John B. Wallingford, Heymut Omran, Jeremy F. Reiter
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.

Graphical abstract

Teaser

Cilia are cellular appendages used for motility and intercellular communication. Sigg et al. reconstruct the evolutionary ancestry of cilia through proteomics of sea urchin, sea anemone, and choanoflagellate cilia. One identified ciliary protein, ENKUR, helps pattern the vertebrate left-right body axis. Humans with inherited mutations in ENKUR have situs inversus.


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