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조경지 지헌영(약리학교실) PLoS Genet
등록일 : 2018-04-02 오후 8:17:00       조회 : 205
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제1저자 조경지(약리학교실, BK21)
교신저자 지헌영(약리학교실, BK21) Friedhelm Hildebrandt(Harvard Medical School)

PLoS Genet. 2018 Mar 30᜚(3):e1007316. doi: 10.1371/journal.pgen.1007316. [Epub ahead of print]
ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-assembly of dynein arms.
Cho KJ1, Noh SH1, Han SM1, Choi WI2, Kim HY1, Yu S1, Lee JS1, Rim JH1, Lee MG1, Hildebrandt F2, Gee HY1.

Author information
1Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea.2Division of Nephrology, Boston Children''s Hospital, Harvard Medical School, Boston, MA, United States of America.

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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