Bizet, Albane A.Becker-Heck, AnitaRyan, RebeccaWeber, KristinaFilhol, EmilieKrug, PaulineHalbritter, JanDelous, MarionLasbennes, Marie-ChristineLinghu, BolanOakeley, Edward J.Zarhrate, MohammedNitschké, PatrickGarfa-Traore, MeriemSerluca, FabrizioYang, FanBouwmeester, TewisPinson, LucileCassuto, ElisabethDubot, PhilippeElshakhs, Neveen A. SolimanSahel, José A.Salomon, RémiDrummond, IainGubler, Marie-ClaireAntignac, CorinneChibout, SalahdineSzustakowski, Joseph D.Hildebrandt, FriedhelmLorentzen, EsbenSailer, Andreas W.Benmerah, AlexandreSaint-Mezard, PierreSaunier, Sophie2016-01-042015Bizet, A. A., A. Becker-Heck, R. Ryan, K. Weber, E. Filhol, P. Krug, J. Halbritter, et al. 2015. “Mutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization.” Nature Communications 6 (1): 8666. doi:10.1038/ncomms9666. http://dx.doi.org/10.1038/ncomms9666.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993556Ciliopathies 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.en-USJournal Article2016-01-0410.1038/ncomms9666