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

Laura Vuolo1, Nicola L Stevenson1, Kate J Heesom2

  • 1Cell Biology Laboratories, School of Biochemistry, University of Bristol, Bristol, United Kingdom.

Elife
|October 16, 2018
PubMed

Insights

The dynein-2 motor

Area of Science:

  • Cell Biology
  • Molecular Motor Function
  • Cilia Biology

Background:

  • Dynein-2 is essential for intraflagellar transport (IFT).
  • Mutations in dynein-2 cause skeletal ciliopathies like Jeune syndrome.
  • Dynein-2 comprises distinct intermediate chains, WDR34 and WDR60.

Purpose of the Study:

  • To elucidate the distinct roles of WDR34 and WDR60 in dynein-2 function.
  • To investigate the impact of WDR34 and WDR60 loss on cilium assembly and IFT.
  • To understand the functional asymmetry within the dynein-2 complex.

Main Methods:

  • Utilized knockout (KO) cell lines for WDR34 and WDR60.
  • Employed quantitative proteomics to analyze motor complex assembly and protein binding.
  • Assessed axoneme extension and transition zone integrity.

Main Results:

  • WDR34 KO cells assemble dynein-2 but fail to extend axonemes, stalling complex function.
  • WDR60 KO cells extend axonemes but show impaired dynein-2 assembly and IFT protein binding.
  • Both WDR34 and WDR60 are crucial for transition zone function and bidirectional IFT.

Conclusions:

  • Functional asymmetry exists between dynein-2 intermediate chains WDR34 and WDR60.
  • Loss of dynein-2 function disrupts transition zone architecture and intraflagellar transport.
  • This study clarifies the specific contributions of dynein-2 subunits to cilium health.
Keywords:
Ciliaaxonemecell biologyciliogenesisdyneinhuman

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