ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-assembly of dynein arms

Kyeong Jee Cho; Shin Hye Noh; Soo Min Han; Won Il Choi; Hye Youn Kim; Seyoung Yu; Joon Suk Lee; John Hoon Rim; Min Goo Lee; Friedhelm Hildebrandt; Heon Yung Gee

doi:10.1371/journal.pgen.1007316

ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-assembly of dynein arms

Kyeong Jee Cho, Shin Hye Noh, Soo Min Han, Won Il Choi, Hye Youn Kim, Seyoung Yu, Joon Suk Lee, John Hoon Rim, Min Goo Lee, Friedhelm Hildebrandt, Heon Yung Gee

Department of Pharmacology

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

Abstract

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.

Original language	English
Article number	e1007316
Journal	PLoS Genetics
Volume	14
Issue number	3
DOIs	https://doi.org/10.1371/journal.pgen.1007316
Publication status	Published - 2018 Mar

Bibliographical note

Funding 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.

Publisher Copyright:
© 2018 Cho et al.

All Science Journal Classification (ASJC) codes

Ecology, Evolution, Behavior and Systematics
Molecular Biology
Genetics
Genetics(clinical)
Cancer Research

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title = "ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-assembly of dynein arms",

abstract = "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.",

author = "Cho, {Kyeong Jee} and Noh, {Shin Hye} and Han, {Soo Min} and Choi, {Won Il} and Kim, {Hye Youn} and Seyoung Yu and Lee, {Joon Suk} and Rim, {John Hoon} and Lee, {Min Goo} and Friedhelm Hildebrandt and Gee, {Heon Yung}",

note = "Funding 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{\textquoteright}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. Publisher Copyright: {\textcopyright} 2018 Cho et al.",

year = "2018",

month = mar,

doi = "10.1371/journal.pgen.1007316",

language = "English",

volume = "14",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "3",

}

ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-assembly of dynein arms. / Cho, Kyeong Jee; Noh, Shin Hye; Han, Soo Min; Choi, Won Il; Kim, Hye Youn; Yu, Seyoung; Lee, Joon Suk; Rim, John Hoon; Lee, Min Goo; Hildebrandt, Friedhelm; Gee, Heon Yung.

In: PLoS Genetics, Vol. 14, No. 3, e1007316, 03.2018.

Research output: Contribution to journal › Article › peer-review

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 - Funding 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. Publisher Copyright: © 2018 Cho et al.

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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DO - 10.1371/journal.pgen.1007316

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JF - PLoS Genetics

SN - 1553-7390

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ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-assembly of dynein arms

Abstract

Bibliographical note

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