PUBLICATION
A mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from the cis-Golgi
- Authors
- Stoetzel, C., Bär, S., De Craene, J.O., Scheidecker, S., Etard, C., Chicher, J., Reck, J.R., Perrault, I., Geoffroy, V., Chennen, K., Strähle, U., Hammann, P., Friant, S., Dollfus, H.
- ID
- ZDB-PUB-161125-3
- Date
- 2016
- Source
- Nature communications 7: 13586 (Journal)
- Registered Authors
- Etard, Christelle, Strähle, Uwe
- Keywords
- Ciliogenesis, Disease genetics, Golgi, Mechanisms of disease
- MeSH Terms
-
- Abnormalities, Multiple/genetics
- Adolescent
- Animals
- Carrier Proteins/metabolism*
- Case-Control Studies
- Cells, Cultured
- Child
- Child, Preschool
- Cilia/metabolism*
- Ciliopathies/genetics*
- Craniofacial Abnormalities/complications
- Craniofacial Abnormalities/genetics
- Female
- Fibroblasts/metabolism
- Golgi Apparatus/metabolism*
- Hand Deformities, Congenital/complications
- Hand Deformities, Congenital/genetics
- Humans
- Learning Disabilities/complications
- Learning Disabilities/genetics
- Male
- Mutation
- Mutation, Missense
- Renal Insufficiency/complications
- Renal Insufficiency/genetics
- Retinitis Pigmentosa/complications
- Retinitis Pigmentosa/genetics
- Saccharomyces cerevisiae
- Siblings
- Skin/cytology
- Vacuolar Sorting Protein VPS15/genetics*
- Young Adult
- Zebrafish
- PubMed
- 27882921 Full text @ Nat. Commun.
Citation
Stoetzel, C., Bär, S., De Craene, J.O., Scheidecker, S., Etard, C., Chicher, J., Reck, J.R., Perrault, I., Geoffroy, V., Chennen, K., Strähle, U., Hammann, P., Friant, S., Dollfus, H. (2016) A mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from the cis-Golgi. Nature communications. 7:13586.
Abstract
Ciliopathies are a group of diseases that affect kidney and retina among other organs. Here, we identify a missense mutation in PIK3R4 (phosphoinositide 3-kinase regulatory subunit 4, named VPS15) in a family with a ciliopathy phenotype. Besides being required for trafficking and autophagy, we show that VPS15 regulates primary cilium length in human fibroblasts, as well as ciliary processes in zebrafish. Furthermore, we demonstrate its interaction with the golgin GM130 and its localization to the Golgi. The VPS15-R998Q patient mutation impairs Golgi trafficking functions in humanized yeast cells. Moreover, in VPS15-R998Q patient fibroblasts, the intraflagellar transport protein IFT20 is not localized to vesicles trafficking to the cilium but is restricted to the Golgi. Our findings suggest that at the Golgi, VPS15 and GM130 form a protein complex devoid of VPS34 to ensure the IFT20-dependent sorting and transport of membrane proteins from the cis-Golgi to the primary cilium.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping