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The microtubule affinity regulating kinase MARK4 promotes axoneme extension during early ciliogenesis

Stefanie Kuhns1, Kerstin N Schmidt, Jürgen Reymann

  • 1Molecular Biology of Centrosomes and Cilia group, Department of Cell and Molecular Biology, Medical Faculty Mannheim, Heidelberg University, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.

The Journal of Cell Biology
|February 13, 2013
PubMed

Insights

Microtubule-associated protein/microtubule affinity regulating kinase 4 (MARK4) is crucial for initiating cilia formation. MARK4 and ODF2 regulate early axoneme extension by influencing the removal of inhibitory complexes from the mother centriole.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Cilia are vital for embryonic development and human health.
  • Key regulators of cilia formation remain largely unidentified.
  • Microtubule-associated protein/microtubule affinity regulating kinase 4 (MARK4) is a potential regulator.

Purpose of the Study:

  • To identify novel regulators of cilia formation.
  • To investigate the role of MARK4 in ciliogenesis.
  • To elucidate the molecular mechanism of MARK4 in cilia assembly.

Main Methods:

  • Functional RNA interference-based screen to identify protein kinases involved in ciliogenesis.
  • Cellular and biochemical analyses (immunofluorescence, Western blotting, ultrastructural analysis) in human and murine cell lines.
  • Knockdown studies to assess the function of MARK4 and ODF2.

Main Results:

  • A screen identified 30 novel protein kinases linked to ciliogenesis.
  • MARK4 localizes to the basal body and ciliary axoneme.
  • MARK4 kinase activity is essential for initiating axoneme extension.
  • ODF2 is an interaction partner of MARK4, and its centriolar localization depends on MARK4.
  • MARK4 and ODF2 regulate the removal of the CP110-Cep97 inhibitory complex, acting at the level of axonemal extension initiation.

Conclusions:

  • MARK4 is a critical positive regulator of early ciliogenesis.
  • MARK4 and ODF2 play essential roles in the initiation of axoneme extension.
  • These findings provide new insights into the molecular mechanisms governing cilia formation.

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