RT Journal Article
SR Electronic
T1 Evolutionary proteomics uncovers ciliary signaling components
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 153437
DO 10.1101/153437
A1 Monika Abedin Sigg
A1 Tabea Menchen
A1 Jeffery Johnson
A1 Chanjae Lee
A1 Semil P. Choksi
A1 Galo Garcia, 3rd
A1 Henriette Busengdal
A1 Gerard Dougherty
A1 Petra Pennekamp
A1 Claudius Werner
A1 Fabian Rentzsch
A1 Nevan Krogan
A1 John B. Wallingford
A1 Heymut Omran
A1 Jeremy F. Reiter
YR 2017
UL http://biorxiv.org/content/early/2017/06/22/153437.abstract
AB Cilia are organelles specialized for movement and signaling. To infer when during animal evolution signaling pathways became associated with cilia, we characterized the proteomes of cilia from three organisms: sea urchins, sea anemones and choanoflagellates. From these ciliomes, we identified 437 high confidence ciliary candidate proteins conserved in mammals, including known regulators of Hh, GPCR and TRP channel signaling. The phylogenetic profiles of their ciliary association indicate that the Hh and GPCR pathways were linked to cilia before the origin of bilateria and TRP channels before the origin of animals. We demonstrated that some of the candidates not previously implicated in ciliary biology localized to cilia and further investigated ENKUR, a TRP channel-interacting protein that we identified in the cilia of all three organisms. In animals, ENKUR is expressed by cells with motile cilia, ENKUR localizes to cilia in diverse organisms and, in both Xenopus laevis and mice, ENKUR is required for patterning the left/right axis. 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 Hh, GPCR and TRP channel signaling, and uncovers a novel ciliary protein that controls vertebrate development and human disease.