Bizet, Albane, Becker-Heck, Anita, Ryan, Rebecca, Weber, Kristina, Filhol, Emilie, Krug, Pauline, Halbritter, Jan, Linghu, Bolan, Oakeley, Edward James, Bole-Feysot, Christine, Nitschke, Patrick, Serluca-Aegerter, Fabrizio, Schmidt, Swetlana, Lasbennes-Eckerlen, Marie-Christine, Damask, Amy, Yang, Fan, Bouwmeester, Antonius, Valette, Huguette, Pinson, Lucile, Cassuto, Elisabeth, Dubot, Philippe, Soliman, Neveen, Sahel, Jose, Salomon, Remi, Antignac, Corinne, Gubler, Marie-Claire, Chibout, Salah-Dine, Szustakowski, Joseph, Hildebrandt, Friedhelm, Lorentzen, Esben, Sailer, Andreas, Benmerah, Alexandre, 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