Zinc finger MYND-type-containing 10 (ZMYND10), a cytoplasmic protein expressed in ciliated cells, causes primary ciliary dyskinesia (PCD) when mutated; however, its function is poorly understood. Therefore, in this study, we examined the roles of ZMYND10 using Zmynd10–/–mice exhibiting typical PCD phenotypes, including hydrocephalus and laterality defects. In these mutants, morphology, the number of motile cilia, and the 9+2 axoneme structure were normal; however, inner and outer dynein arms (IDA and ODA, respectively) were absent. ZMYND10 interacted with ODA components and proteins, including LRRC6, DYX1C1, and C21ORF59, implicated in the cytoplasmic pre-assembly of DAs, whose levels were significantly reduced in Zmynd10–/–mice. LRRC6 and DNAI1 were more stable when co-expressed with ZYMND10 than when expressed alone. DNAI2, which did not interact with ZMYND10, was not stabilized by co-expression with ZMYND10 alone, but was stabilized by co-expression with DNAI1 and ZMYND10, suggesting that ZMYND10 stabilized DNAI1, which subsequently stabilized DNAI2. Together, these results demonstrated that ZMYND10 regulated the early stage of DA cytoplasmic pre-assembly by stabilizing DNAI1.
Bibliographical noteFunding Information:
FH was supported by grants from the National Institutes of Health (nos. DK076683 and DK068306). HYG was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health & Welfare, Republic of Korea (no. H15C2892). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. F.H. is a William E. Harmon professor. We thank Yonsei Advanced Imaging Center along with Carl Zeiss Microscopy, Harvard Medical School Electron Microscopy Facility (Maria Ericsson), and Transgenic Animal Model Core of the University of Michigan’s Biomedical Core Facilities (Thomas L. Saunders and Elizabeth Hughes) for technical assistance. We also thank Dr. Hiroshi Hamada (Osaka University) for sharing the LRRC6 and DNAH5 antibodies.
© 2018 Cho et al.
All Science Journal Classification (ASJC) codes
- Ecology, Evolution, Behavior and Systematics
- Molecular Biology
- Cancer Research