Related Experiment Video
Updated: May 9, 2026
High-speed Video Microscopy Analysis for First-line Diagnosis of Primary Ciliary Dyskinesia
Published on: January 19, 2022
ZMYND10 is mutated in primary ciliary dyskinesia and interacts with LRRC6
Maimoona A Zariwala1, Heon Yung Gee, Małgorzata Kurkowiak
1Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Abstract:
Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function.
Insights
Genetic defects in ZMYND10 and LRRC6 cause primary ciliary dyskinesia (PCD), a condition leading to respiratory infections and infertility. These proteins interact and are crucial for motile cilia function and assembly.
Area of Science:
- Genetics
- Cell Biology
- Molecular Biology
Background:
- Primary ciliary dyskinesia (PCD) is a genetic disorder affecting motile cilia, causing recurrent respiratory infections and male infertility.
- The genetic underpinnings of PCD are complex, with mutations in various genes implicated in ciliary structure and function.
Purpose of the Study:
- To identify the genetic causes of primary ciliary dyskinesia (PCD) in families.
- To investigate the functional relationship between ZMYND10 and LRRC6 in the context of motile cilia.
Main Methods:
- Whole-exome resequencing and high-throughput mutation analysis were employed to identify causative genes.
- Protein interaction studies, immunofluorescence, and animal model experiments (zebrafish and Xenopus) were conducted.
Main Results:
- Recessive biallelic mutations in ZMYND10 and LRRC6 were identified in multiple PCD families.
- ZMYND10 and LRRC6 were found to interact, colocalize with centriole markers, and their mutations disrupted this interaction.
- ZMYND10 mutations led to the absence of key axonemal proteins in respiratory cilia, and animal models showed ciliary defects.
Conclusions:
- A cytoplasmic protein complex of ZMYND10 and LRRC6 is essential for motile ciliary function.
- Mutations in ZMYND10 and LRRC6 represent a significant cause of primary ciliary dyskinesia.
- Understanding this complex provides insights into ciliary assembly and human genetic disorders.
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
01:05Mechanism of Ciliary Motion
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...
01:09Cytoskeletal Linker Proteins - Plakins
01:22Microtubules in Signaling