PUBLICATION
Mutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization
- Authors
- Bizet, A.A., Becker-Heck, A., Ryan, R., Weber, K., Filhol, E., Krug, P., Halbritter, J., Delous, M., Lasbennes, M.C., Linghu, B., Oakeley, E.J., Zarhrate, M., Nitschké, P., Garfa-Traore, M., Serluca, F., Yang, F., Bouwmeester, T., Pinson, L., Cassuto, E., Dubot, P., Elshakhs, N.A., Sahel, J.A., Salomon, R., Drummond, I.A., Gubler, M.C., Antignac, C., Chibout, S., Szustakowski, J.D., Hildebrandt, F., Lorentzen, E., Sailer, A.W., Benmerah, A., Saint-Mezard, P., Saunier, S.
- ID
- ZDB-PUB-151022-2
- Date
- 2015
- Source
- Nature communications 6: 8666 (Journal)
- Registered Authors
- Delous, Marion, Drummond, Iain, Ryan, Rebecca, Saunier, Sophie, Serluca, Fabrizio, Yang, Fan
- Keywords
- Cell signalling, Microtubules, Mutation
- MeSH Terms
-
- Animals
- Blotting, Western
- Carrier Proteins/genetics*
- Carrier Proteins/metabolism
- Cell Polarity/genetics
- Circular Dichroism
- Embryo, Nonmammalian
- Female
- Fluorescent Antibody Technique
- Gene Knockout Techniques
- HEK293 Cells
- High-Throughput Nucleotide Sequencing
- Humans
- Immunoprecipitation
- Kidney Diseases, Cystic/genetics*
- Kidney Diseases, Cystic/metabolism
- Male
- Microphthalmos/genetics
- Microtubule-Associated Proteins/genetics*
- Microtubule-Associated Proteins/metabolism*
- Microtubules/metabolism*
- Mutation*
- Pedigree
- Retinal Degeneration/genetics*
- Retinal Degeneration/metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Zebrafish
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 26487268 Full text @ Nat. Commun.
Citation
Bizet, A.A., Becker-Heck, A., Ryan, R., Weber, K., Filhol, E., Krug, P., Halbritter, J., Delous, M., Lasbennes, M.C., Linghu, B., Oakeley, E.J., Zarhrate, M., Nitschké, P., Garfa-Traore, M., Serluca, F., Yang, F., Bouwmeester, T., Pinson, L., Cassuto, E., Dubot, P., Elshakhs, N.A., Sahel, J.A., Salomon, R., Drummond, I.A., Gubler, M.C., Antignac, C., Chibout, S., Szustakowski, J.D., Hildebrandt, F., Lorentzen, E., Sailer, A.W., Benmerah, A., Saint-Mezard, P., Saunier, S. (2015) Mutations in TRAF3IP1/IFT54 reveal a new role for IFT proteins in microtubule stabilization. Nature communications. 6:8666.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping