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Centrosome and ciliary abnormalities in fetal akinesia deformation sequence human fibroblasts
- Source :
- Scientific Reports, Scientific Reports, Vol 10, Iss 1, Pp 1-16 (2020)
- Publication Year :
- 2020
-
Abstract
- Ciliopathies are clinical disorders of the primary cilium with widely recognised phenotypic and genetic heterogeneity. Here we found impaired ciliogenesis in fibroblasts derived from individuals with fetal akinesia deformation sequence (FADS), a broad spectrum of neuromuscular disorders arising from impaired foetal movement. We show that cells derived from FADS individuals have shorter and less primary cilia (PC), in association with alterations in post-translational modifications in α-tubulin. Similarly, siRNA-mediated depletion of two known FADS proteins, the scaffold protein rapsyn and the nucleoporin NUP88, resulted in defective PC formation. Consistent with a role in ciliogenesis, rapsyn and NUP88 localised to centrosomes and PC. By proximity-ligation assays, we show that rapsyn and NUP88 are adjacent and that both proteins are adjoining to all three tubulin isoforms (α, and γ rapsyn-NUP88 interface, as well as their contact to microtubules, is perturbed in the examined FADS cells. We suggest that the perturbed rapsyn-NUP88-tubulin interface leads to defects in PC formation and that defective ciliogenesis contributes to the pleiotropic defects seen in FADS.SummaryFibroblasts derived from fetal akinesia individuals are characterised by ciliary defects and rapsyn and NUP88 are required for proper formation of the primary cilium.
- Subjects :
- Scaffold protein
Molecular biology
TUBULIN
lcsh:Medicine
Muscle Proteins
Ciliopathies
Microtubules
Nuclear envelope
DOMAIN
Tubulin
Image Processing, Computer-Assisted
Protein Isoforms
RNA, Small Interfering
Super-resolution microscopy
lcsh:Science
Cytoskeleton
MUTATION
Cellular Senescence
Cell proliferation
Arthrogryposis
Multidisciplinary
Microscopy, Confocal
Cilium
Phenotype
Cell biology
Multidisciplinary Sciences
Mechanisms of disease
Science & Technology - Other Topics
Nucleoporin
Biology
Cellular imaging
Transfection
Article
Microtubule
Ciliogenesis
Developmental biology
Humans
Abnormalities, Multiple
NICOTINIC ACETYLCHOLINE-RECEPTOR
Cilia
CILIOGENESIS
Cell Nucleus
Centrosome
Nuclear organization
Science & Technology
PROTEIN RAPSYN
COMPLEX
lcsh:R
PATHWAYS
Fibroblasts
TRANSPORT
Nuclear Pore Complex Proteins
biology.protein
lcsh:Q
Protein Processing, Post-Translational
MUSK
Post-translational modifications
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 10
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....3076856c02066a00e66a36f5f97eb11a