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Mutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization

Bizet, Albane and Becker-Heck, Anita and Ryan, Rebecca and Weber, Kristina and Filhol, Emilie and Krug, Pauline and Halbritter, Jan and Linghu, Bolan and Oakeley, Edward James and Bole-Feysot, Christine and Nitschke, Patrick and Serluca-Aegerter, Fabrizio and Schmidt, Swetlana and Lasbennes-Eckerlen, Marie-Christine and Damask, Amy and Yang, Fan and Bouwmeester, Antonius and Valette, Huguette and Pinson, Lucile and Cassuto, Elisabeth and Dubot, Philippe and Soliman, Neveen and Sahel, Jose and Salomon, Remi and Antignac, Corinne and Gubler, Marie-Claire and Chibout, Salah-Dine and Szustakowski, Joseph and Hildebrandt, Friedhelm and Lorentzen, Esben and Sailer, Andreas and Benmerah, Alexandre and Saint-Mezard, Pierre and Saunier, Sophie (2015) Mutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization. Nat Comm. pp. 1-14. ISSN 2041-1723 (Electronic); 2041-1723 (Linking)

Abstract

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.

Item Type: Article
Additional Information: Unmapped bibliographic data: C6 - Nihms724272 [EPrints field already has value set] LA - eng [Field not mapped to EPrints] ET - 2015/10/22 [Field not mapped to EPrints] ST - Mutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization [Field not mapped to EPrints] AU - Bizet, A. A. [Field not mapped to EPrints] AU - Becker-Heck, A. [Field not mapped to EPrints] AU - Ryan, R. [Field not mapped to EPrints] AU - Weber, K. [Field not mapped to EPrints] AU - Filhol, E. [Field not mapped to EPrints] AU - Krug, P. [Field not mapped to EPrints] AU - Halbritter, J. [Field not mapped to EPrints] AU - Delous, M. [Field not mapped to EPrints] AU - Lasbennes, M. C. [Field not mapped to EPrints] AU - Linghu, B. [Field not mapped to EPrints] AU - Oakeley, E. J. [Field not mapped to EPrints] AU - Zarhrate, M. [Field not mapped to EPrints] AU - Nitschke, P. [Field not mapped to EPrints] AU - Garfa-Traore, M. [Field not mapped to EPrints] AU - Serluca, F. [Field not mapped to EPrints] AU - Yang, F. [Field not mapped to EPrints] AU - Bouwmeester, T. [Field not mapped to EPrints] AU - Pinson, L. [Field not mapped to EPrints] AU - Cassuto, E. [Field not mapped to EPrints] AU - Dubot, P. [Field not mapped to EPrints] AU - Elshakhs, N. A. [Field not mapped to EPrints] AU - Sahel, J. A. [Field not mapped to EPrints] AU - Salomon, R. [Field not mapped to EPrints] AU - Drummond, I. A. [Field not mapped to EPrints] AU - Gubler, M. C. [Field not mapped to EPrints] AU - Antignac, C. [Field not mapped to EPrints] AU - Chibout, S. [Field not mapped to EPrints] AU - Szustakowski, J. D. [Field not mapped to EPrints] AU - Hildebrandt, F. [Field not mapped to EPrints] AU - Lorentzen, E. [Field not mapped to EPrints] AU - Sailer, A. W. [Field not mapped to EPrints] AU - Benmerah, A. [Field not mapped to EPrints] AU - Saint-Mezard, P. [Field not mapped to EPrints] AU - Saunier, S. [Field not mapped to EPrints] C2 - PMC4617596 [Field not mapped to EPrints] AD - Inserm UMR-1163, Laboratory of Hereditary Kidney Diseases, 75015 Paris, France. [Field not mapped to EPrints] DP - NLM [Field not mapped to EPrints] AN - 26487268 [Field not mapped to EPrints]
Keywords: Ciliopathies, kidney disease, human genetics,
Date Deposited: 01 Mar 2017 00:45
Last Modified: 01 Mar 2017 00:45
URI: https://oak.novartis.com/id/eprint/24673

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