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Updated: Sep 18, 2025

High-speed Video Microscopy Analysis for First-line Diagnosis of Primary Ciliary Dyskinesia
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High-speed Video Microscopy Analysis for First-line Diagnosis of Primary Ciliary Dyskinesia

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Molecular Insights into Outer Dynein Arm Defects in Primary Ciliary Dyskinesia: Involvement of ZMYND10 and GRP78

İlker Levent Erdem1, Zeynep Bengisu Kaya2, Pergin Atilla1

  • 1Department of Histology and Embryology, Hacettepe University Faculty of Medicine, 06230 Ankara, Turkey.

Cells
|June 25, 2025
PubMed
Abstract

Insights

Primary ciliary dyskinesia (PCD) involves ciliary defects and infections. This study links DNAH5, ZMYND10, and GRP78 protein alterations with metabolic changes, suggesting cellular stress in PCD patients.

Area of Science:

  • Genetics and Molecular Biology
  • Cell Biology
  • Metabolomics

Background:

  • Primary ciliary dyskinesia (PCD) is a rare genetic disorder causing recurrent sinopulmonary infections due to defective motile cilia.
  • PCD exhibits genetic heterogeneity, often involving structural ciliary protein abnormalities.
  • Zinc finger MYND-type containing 10 (ZMYND10) is crucial for outer dynein arm assembly, with chaperones like Glucose-regulated protein 78 (GRP78) aiding protein folding.

Purpose of the Study:

  • To investigate mutations in ZMYND10 and Dynein axonemal heavy chain 5 (DNAH5) in individuals diagnosed with PCD.
  • To analyze the correlation between DNAH5 abnormalities and preassembly/chaperone proteins.

Main Methods:

  • Eight individuals (aged 14-22) with clinical PCD symptoms and confirmed DNAH5 mutations were studied.
  • Immunofluorescence labeling of nasal swabs (DNAH5-β-tubulin, β-tubulin-ZMYND10, β-tubulin-GRP78) was performed.
  • Serum metabolomics and proteomics were assessed to identify metabolic alterations.

Main Results:

  • Significant differences in DNAH5, ZMYND10, and GRP78 corrected total cell fluorescence (CTCF) levels were observed between PCD patients and controls.
  • Metabolomic analysis revealed decreased biosynthesis of valine, leucine, and isoleucine.
  • Increased biosynthesis of malate and triacylglycerol, altered shuttle activity (malate-aspartate, glycerol phosphate), and changes in arginine/proline metabolism indicated mitochondrial and ER stress.

Conclusions:

  • Altered expression of DNAH5, ZMYND10, and GRP78, coupled with metabolic shifts, suggests a complex interplay between ciliary dysfunction and cellular stress in PCD.
  • Further research is warranted to elucidate the precise mechanisms underlying these observations.
Keywords:
DNAH5GRP78ODAPCDZMYND10ciliopathyimmunofluorescencemetabolomicsproteomics

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