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Norway

PMID:29601588  

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
PLoS genetics | 2018

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.

Pubmed ID: 29601588

Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK068306
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK076683

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