Loss-of-function variants in ODAD1 disrupt ODA docking and induce actin cytoskeletal remodeling in primary ciliary dyskinesia - PubMed
18 hours ago
- #ciliary dyskinesia
- #actin cytoskeleton
- #ODAD1
- ODAD1 loss-of-function variants impair outer dynein arm docking, leading to defective ciliary beating.
- Patients with homozygous ODAD1 variants show hallmark PCD symptoms, low nasal nitric oxide, and situs inversus.
- ODAD1 deficiency reduces multiciliated cell abundance, disrupts basal body orientation, and impairs multiciliogenesis.
- Proteomics and imaging reveal actin cytoskeletal remodeling, with aberrant F-actin bundling in epithelial layers.
- Pharmacological inhibition of actin polymerization partially rescues multiciliated cell defects.
- Wild-type ODAD1 re-expression in organoids restores outer dynein arm assembly and ciliary beating.