Evolutionary Proteomics Uncovers Ancient Associations of Cilia with Signaling Pathways.
Dev Cell
; 43(6): 744-762.e11, 2017 12 18.
Article
em En
| MEDLINE
| ID: mdl-29257953
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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação a Calmodulina
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Cílios
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Proteínas Adaptadoras de Transdução de Sinal
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article