Open AccessZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-assembly of dynein arms
Author(s) -
Kyeong Jee Cho,
Shin Hye Noh,
Seung Baik Han,
WonIl Choi,
Hye Youn Kim,
Seyoung Yu,
Joon Suk Lee,
John Hoon Rim,
Min Goo Lee,
Friedhelm Hildebrandt,
Heon Yung Gee
Publication year - 2018
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1007316
Subject(s) - biology , axoneme , cytoplasm , microbiology and biotechnology , cilium , dynein , ciliogenesis , mutant , phenotype , primary ciliary dyskinesia , mutation , microtubule , genetics , flagellum , gene , linguistics , philosophy , bronchiectasis , lung
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.