Dynein-2 intermediate chains play crucial but distinct roles in primary cilia formation and function

Elife. 2018 Oct 16;7:e39655. doi: 10.7554/eLife.39655.


The dynein-2 microtubule motor is the retrograde motor for intraflagellar transport. Mutations in dynein-2 components cause skeletal ciliopathies, notably Jeune syndrome. Dynein-2 contains a heterodimer of two non-identical intermediate chains, WDR34 and WDR60. Here, we use knockout cell lines to demonstrate that each intermediate chain has a distinct role in cilium function. Using quantitative proteomics, we show that WDR34 KO cells can assemble a dynein-2 motor complex that binds IFT proteins yet fails to extend an axoneme, indicating complex function is stalled. In contrast, WDR60 KO cells do extend axonemes but show reduced assembly of dynein-2 and binding to IFT proteins. Both proteins are required to maintain a functional transition zone and for efficient bidirectional intraflagellar transport. Our results indicate that the subunit asymmetry within the dynein-2 complex is matched with a functional asymmetry between the dynein-2 intermediate chains. Furthermore, this work reveals that loss of function of dynein-2 leads to defects in transition zone architecture, as well as intraflagellar transport.

Keywords: Cilia; axoneme; cell biology; ciliogenesis; dynein; human.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • CRISPR-Cas Systems / genetics
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cell Membrane / metabolism
  • Cilia / metabolism*
  • Cilia / ultrastructure
  • Dyneins / metabolism*
  • Gene Knockout Techniques
  • Humans
  • Mice
  • Mutation / genetics
  • Phenotype
  • Tumor Suppressor Proteins / metabolism


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • IFT88 protein, human
  • Tumor Suppressor Proteins
  • WDR34 protein, human
  • WDR60 protein, human
  • Dyneins