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Dev Cell. 2014 Mar 10;28(5):483-96. doi: 10.1016/j.devcel.2014.01.021. Epub 2014 Feb 27.

EFCAB7 and IQCE regulate hedgehog signaling by tethering the EVC-EVC2 complex to the base of primary cilia.

Author information

1
Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
2
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
3
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. Electronic address: aravind@ncbi.nlm.nih.gov.
4
Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: rrohatgi@stanford.edu.

Abstract

The Hedgehog (Hh) pathway depends on primary cilia in vertebrates, but the signaling machinery within cilia remains incompletely defined. We report the identification of a complex between two ciliary proteins, EFCAB7 and IQCE, which positively regulates the Hh pathway. The EFCAB7-IQCE module anchors the EVC-EVC2 complex in a signaling microdomain at the base of cilia. EVC and EVC2 genes are mutated in Ellis van Creveld and Weyers syndromes, characterized by impaired Hh signaling in skeletal, cardiac, and orofacial tissues. EFCAB7 binds to a C-terminal disordered region in EVC2 that is deleted in Weyers patients. EFCAB7 depletion mimics the Weyers cellular phenotype-the mislocalization of EVC-EVC2 within cilia and impaired activation of the transcription factor GLI2. Evolutionary analysis suggests that emergence of these complexes might have been important for adaptation of an ancient organelle, the cilium, for an animal-specific signaling network.

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PMID:
24582806
PMCID:
PMC4027042
DOI:
10.1016/j.devcel.2014.01.021
[Indexed for MEDLINE]
Free PMC Article

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