Cho, Kyeong JeeNoh, Shin HyeHan, Soo MinChoi, Won-IlKim, Hye-YounYu, SeyoungLee, Joon SukRim, John HoonLee, Min GooHildebrandt, FriedhelmGee, Heon Yung2018-06-272018Cho, K. J., S. H. Noh, S. M. Han, W. Choi, H. Kim, S. Yu, J. S. Lee, et al. 2018. “ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-assembly of dynein arms.” PLoS Genetics 14 (3): e1007316. doi:10.1371/journal.pgen.1007316. http://dx.doi.org/10.1371/journal.pgen.1007316.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37160237Zinc 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.en-USBiology and Life SciencesBiochemistryProteinsCytoskeletal ProteinsDyneinsCell BiologyMolecular MotorsMicrotubule MotorsMotor ProteinsCellular Structures and OrganellesCiliaImmunologic TechniquesImmunoassaysImmunofluorescenceAnatomyRespiratory SystemTracheaMedicine and Health SciencesCytoplasmPrecipitation TechniquesImmunoprecipitationCo-ImmunoprecipitationMolecular BiologyMolecular Biology TechniquesMolecular Probe TechniquesImmunoblottingJournal Article2018-06-2710.1371/journal.pgen.1007316