2. Academic Validation
  3. The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells

The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells

  • Nat Commun. 2014 Aug 19:5:4585. doi: 10.1038/ncomms5585.
Thibaut Eguether 1,  Maria A Ermolaeva 2,  Yongge Zhao 3,  Marion C Bonnet 4,  Ashish Jain 3,  Manolis Pasparakis 2,  Gilles Courtois 5,  Anne-Marie Tassin 6
Affiliations

Affiliations

  • 1 1] Institut Curie/INSERM U759, Campus Universitaire, Bat 112, 91405 Orsay Cedex, France [2] Université Pierre et Marie Curie, 75005 Paris, France [3].
  • 2 Institute for Genetics, Center for Molecular Medicine (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany.
  • 3 Laboratory of Host Defenses, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • 4 1] Institute for Genetics, Center for Molecular Medicine (CMMC) and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany [2] Excellence Research Chair, Université Européenne de Bretagne, IRSET/INSERM UMR1085, Faculté de Pharmacie, Université de Rennes 1, 35000 Rennes, France.
  • 5 1] Université Grenoble Alpes, 38000 Grenoble, France [2] INSERM U1038/BGE/Institut de Recherches en Technologies et Sciences pour le Vivant, CEA, 38054 Grenoble, France.
  • 6 1] Institut Curie/INSERM U759, Campus Universitaire, Bat 112, 91405 Orsay Cedex, France [2] CNRS, Centre de Génétique Moléculaire, UPR3404, Avenue de la Terrasse, F-91198 Gif-sur-Yvette, France.
PMID: 25134987 DOI: 10.1038/ncomms5585
Abstract

CYLD is a tumour suppressor gene mutated in familial cylindromatosis, a genetic disorder leading to the development of skin appendage tumours. It encodes a deubiquitinating Enzyme that removes Lys63- or linear-linked ubiquitin chains. CYLD was shown to regulate cell proliferation, cell survival and inflammatory responses, through various signalling pathways. Here we show that CYLD localizes at centrosomes and basal bodies via interaction with the centrosomal protein CAP350 and demonstrate that CYLD must be both at the centrosome and catalytically active to promote ciliogenesis independently of NF-κB. In transgenic mice engineered to mimic the smallest truncation found in cylindromatosis patients, CYLD interaction with CAP350 is lost disrupting CYLD centrosome localization, which results in cilia formation defects due to impairment of basal body migration and docking. These results point to an undiscovered regulation of ciliogenesis by Lys63 ubiquitination and provide new perspectives regarding CYLD function that should be considered in the context of cylindromatosis.

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