TY - JOUR
T1 - ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-assembly of dynein arms
AU - Cho, Kyeong Jee
AU - Noh, Shin Hye
AU - Han, Soo Min
AU - Choi, Won Il
AU - Kim, Hye Youn
AU - Yu, Seyoung
AU - Lee, Joon Suk
AU - Rim, John Hoon
AU - Lee, Min Goo
AU - Hildebrandt, Friedhelm
AU - Gee, Heon Yung
N1 - Publisher Copyright:
© 2018 Cho et al.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pgen.1007316
DO - 10.1371/journal.pgen.1007316
M3 - Article
C2 - 29601588
AN - SCOPUS:85044816397
VL - 14
JO - PLoS Genetics
JF - PLoS Genetics
SN - 1553-7390
IS - 3
M1 - e1007316
ER -