Adolescent idiopathic scoliosis associated POC5 mutation impairs cell cycle, cilia length and centrosome protein interactions

Abstract : Adolescent Idiopathic Scoliosis (AIS) is a spinal deformity that affects approximately 3 percent of human adolescents. Although the etiology and molecular basis of AIS is unclear, several genes such as POC5 have been identified as possible causes of the condition. In order to understand the role of POC5 in the pathogenesis of AIS, we investigated the subcellular localization of POC5 in cilia of cells over-expressing either the wild type (wt) or an AIS-related POC5 variant POC5A429V. Mutation of POC5 was found to alter its subcellular localization and to induce ciliary retraction. Furthermore, we observed an impaired cell-cycle progression with the accumulation of cells in the S-phase in cells expressing POC5A429V. Using immunoprecipitation coupled to mass spectrometry, we identified specific protein interaction partners of POC5, most of which were components of cilia and cytoskeleton. Several of these interactions were altered upon mutation of POC5. Altogether, our results demonstrate major cellular alterations, disturbances in centrosome protein interactions and cilia retraction in cells expressing an AIS-related POC5 mutation. Our study suggests that defects in centrosomes and cilia may underlie AIS pathogenesis.
Document type :
Journal articles
Complete list of metadatas

Cited literature [38 references]  Display  Hide  Download

https://hal-riip.archives-ouvertes.fr/pasteur-02133010
Contributor : Michel Courcelles <>
Submitted on : Friday, May 17, 2019 - 5:59:22 PM
Last modification on : Thursday, August 22, 2019 - 2:34:03 PM

File

Adolescent_idiopathic_scoliasi...
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

Amani Hassan, Stefan Parent, Hélène Mathieu, Charlotte Zaouter, Sirinart Molidperee, et al.. Adolescent idiopathic scoliosis associated POC5 mutation impairs cell cycle, cilia length and centrosome protein interactions. PLoS ONE, Public Library of Science, 2019, 14 (3), pp.e0213269. ⟨10.1371/journal.pone.0213269⟩. ⟨pasteur-02133010⟩

Share

Metrics

Record views

8

Files downloads

14