Mutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization
| Autor: | Bolan Linghu, Pierre Saint-Mezard, Fan Yang, Marion Delous, Anita Becker-Heck, Joseph D. Szustakowski, Fabrizio C. Serluca, Jan Halbritter, Alexandre Benmerah, Mohammed Zarhrate, Rebecca Ryan, Albane A. Bizet, Elisabeth Cassuto, Kristina Weber, Esben Lorentzen, Marie-Christine Lasbennes, Neveen A. Soliman Elshakhs, Philippe Dubot, Sophie Saunier, Patrick Nitschke, Pauline Krug, Andreas W. Sailer, Edward J. Oakeley, Corinne Antignac, Emilie Filhol, Rémi Salomon, José Sahel, Friedhelm Hildebrandt, Meriem Garfa-Traore, Marie-Claire Gubler, Iain A. Drummond, Tewis Bouwmeester, Salah-Dine Chibout, Lucile Pinson |
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| Přispěvatelé: | Benmerah, Alexandre, Molecular bases of hereditary kidney diseases: nephronophthisis and hypodysplasia (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Novartis Institutes for BioMedical Research (NIBR), Max-Planck-Institut für Biochemie = Max Planck Institute of Biochemistry (MPIB), Max-Planck-Gesellschaft, Harvard Medical School [Boston] (HMS), Universitätsklinikum Leipzig [Germany] (UKL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier Chalon-sur-Saône William Morey, Cairo University, Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Centre d'investigation clinique Quinze-Vingts [CHNO] (CIC1423 - CIC QUINZE-VINGTS), Institut Hospitalo-Universitaire FOReSIGHT, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Massachusetts General Hospital [Boston] |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Embryo Nonmammalian Fluorescent Antibody Technique General Physics and Astronomy [SDV.GEN] Life Sciences [q-bio]/Genetics Microtubules [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology Ciliopathies Gene Knockout Techniques 0302 clinical medicine Microphthalmos [SDV.BDD]Life Sciences [q-bio]/Development Biology Zebrafish 0303 health sciences Multidisciplinary biology Reverse Transcriptase Polymerase Chain Reaction Circular Dichroism Cilium Retinal Degeneration Cell Polarity High-Throughput Nucleotide Sequencing Kidney Diseases Cystic Pedigree 3. Good health Cell biology Female Microtubule-Associated Proteins Blotting Western [SDV.BC]Life Sciences [q-bio]/Cellular Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Microtubule Nephronophthisis Ciliogenesis [SDV.BDD] Life Sciences [q-bio]/Development Biology medicine Animals Humans Immunoprecipitation [SDV.BC] Life Sciences [q-bio]/Cellular Biology Cytoplasmic microtubule 030304 developmental biology [SDV.GEN]Life Sciences [q-bio]/Genetics General Chemistry Zebrafish Proteins medicine.disease biology.organism_classification [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology Molecular biology Ciliopathy HEK293 Cells Mutation Carrier Proteins 030217 neurology & neurosurgery |
| Zdroj: | NATURE COMMUNICATIONS Aarhus University Nature Communications Nature Communications, 2015, 6 (1), pp.8666. ⟨10.1038/ncomms9666⟩ |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms9666⟩ |
| Popis: | Ciliopathies are a large group of clinically and genetically heterogeneous disorders caused by defects in primary cilia. Here we identified mutations in TRAF3IP1 (TNF Receptor-Associated Factor Interacting Protein 1) in eight patients from five families with nephronophthisis (NPH) and retinal degeneration, two of the most common manifestations of ciliopathies. TRAF3IP1 encodes IFT54, a subunit of the IFT-B complex required for ciliogenesis. The identified mutations result in mild ciliary defects in patients but also reveal an unexpected role of IFT54 as a negative regulator of microtubule stability via MAP4 (microtubule-associated protein 4). Microtubule defects are associated with altered epithelialization/polarity in renal cells and with pronephric cysts and microphthalmia in zebrafish embryos. Our findings highlight the regulation of cytoplasmic microtubule dynamics as a role of the IFT54 protein beyond the cilium, contributing to the development of NPH-related ciliopathies. Nephrophthisis (NPH) is a common manifestation of ciliopathy diseases. Here the authors identify mutations in intraflagellar transport 54 (IFT54) in patients with NPH and discover an extra-ciliary role for IFT54 in regulating cytoplasmic microtubule dynamics, that contributes to the pathophysiology of this disease. |
| Databáze: | OpenAIRE |
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