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

Details

• Alternative Title:
  Dev Cell
• Personal Author:
  Pusapati, Ganesh V. ; Hughes, Casey E ; Dorn, Karolin V. ; Zhang, Dapeng ; Sugianto, Priscilla ; Aravind, L. ; Rohatgi, Rajat
• Description:
  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.
• Subjects:
  Amino Acid Sequence Animals Article Blotting, Western Calcium-Binding Proteins Chromatography, Affinity Cilia Gene Expression Regulation Hedgehog Proteins HEK293 Cells Humans Immunoprecipitation Kruppel-Like Transcription Factors Membrane Proteins Mice Molecular Sequence Data Mutation NIH 3T3 Cells Phenotype Phylogeny Protein Interaction Domains And Motifs Real-Time Polymerase Chain Reaction Receptors, G-Protein-Coupled Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger Sequence Homology, Amino Acid Signal Transduction Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

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• Source:
  Dev Cell. 2014; 28(5):483-496.
• Pubmed ID:
  24582806
• Pubmed Central ID:
  PMC4027042
• Document Type:
  Journal Article
• Funding:
  DP2 GM105448/GM/NIGMS NIH HHS/United States ; DP2GM105448/DP/NCCDPHP CDC HHS/United States ; Intramural NIH HHS/United States
• Volume:
  28
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:b9e668d503b504c3519fafeee773dfe3e889b0fc9064ecb989c76e947e02abda
• Download URL:
  https://stacks.cdc.gov/view/cdc/29962/cdc_29962_DS1.pdf
• File Type:
  [PDF - 3.93 MB ]