Afficher la couverture 'Mutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization | Bizet, Albane' en grand format
/5

0 avis

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

Archive ouverte

Bizet, Albane | Becker-Heck, Anita | Ryan, Rebecca | Weber, Kristina | Filhol, Emilie | Krug, Pauline | Halbritter, Jan | Delous, Marion | Lasbennes, Marie-Christine | Linghu, Bolan | Oakeley, Edward | Zarhrate, Mohammed | Nitschké, Patrick | Garfa-Traore, Meriem | Serluca, Fabrizio | Yang, Fan | Bouwmeester, Tewis | Pinson, Lucile | Cassuto, Elisabeth | Dubot, Philippe | Elshakhs, Neveen | Sahel, José | Salomon, Rémi | Drummond, Iain | Gubler, Marie-Claire | Antignac, Corinne | Chibout, Salahdine | Szustakowski, Joseph | Hildebrandt, Friedhelm | Lorentzen, Esben | Sailer, Andreas | Benmerah, Alexandre | Saint-Mezard, Pierre | Saunier, Sophie

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

Suggestions

Du même auteur

Mutations in MAPKBP1 Cause Juvenile or Late-Onset Cilia-Independent Nephronophthisis

Archive ouverte | Macia, Maxence | CCSD

International audience. Nephronophthisis (NPH), an autosomal-recessive tubulointerstitial nephritis, is the most common cause of hereditary end-stage renal disease in the first three decades of life. Since most NPH ...

The genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies

Archive ouverte | Petzold, Friederike | CCSD

International audience

Mutations of CEP83 Cause Infantile Nephronophthisis and Intellectual Disability

Archive ouverte | Failler, Marion | CCSD

International audience. Ciliopathies are a group of hereditary disorders associated with defects in cilia structure and function. The distal appendages (DAPs) of centrioles are involved in the docking and anchoring ...

Chargement des enrichissements...