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

PLoS Genet. 2018 Mar 30;14(3):e1007316. doi: 10.1371/journal.pgen.1007316. eCollection 2018 Mar.

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.

MeSH terms

  • Animals
  • Axoneme / metabolism
  • Cytoplasm / metabolism*
  • Cytoskeletal Proteins
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dyneins / metabolism*
  • Humans
  • Mice
  • Mice, Knockout
  • Phenotype
  • Proteins / metabolism
  • RNA, Messenger / metabolism

Substances

  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Lrrc6 protein, mouse
  • Proteins
  • RNA, Messenger
  • ZMYND10 protein, mouse
  • Dyneins