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Dev Cell. 2017 Dec 18;43(6):744-762.e11. doi: 10.1016/j.devcel.2017.11.014.

Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways.

Author information

1
Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA.
2
Department of General Pediatrics, University Children's Hospital Muenster, Muenster 48149, Germany.
3
Department of Molecular Biosciences, Center for Systems and Synthetic Biology and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
4
Gladstone Institute of Cardiovascular Disease and Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA.
5
Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
6
Sars International Centre for Marine Molecular Biology, University of Bergen, Bergen 5008, Norway.
7
Gladstone Institute of Cardiovascular Disease and Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
8
Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA. Electronic address: jeremy.reiter@ucsf.edu.

Abstract

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.

KEYWORDS:

GPCR; Hedgehog signaling; TRP channel; choanoflagellate; ciliopathy; cilium; left-right axis patterning; proteomics; sea anemone; sea urchin

PMID:
29257953
PMCID:
PMC5752135
DOI:
10.1016/j.devcel.2017.11.014
[Indexed for MEDLINE]
Free PMC Article

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