Related Experiment Video

Updated: Sep 10, 2025

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
11:23

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein

Published on: June 30, 2019

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Kinase activity of DYRK family members is required for regulating primary cilium length, stability and morphology

Melis D Arslanhan1, Ebru Topçu1, Elif Nur Firat-Karalar2,3

  • 1Department of Molecular Biology and Genetics, Koç University, Istanbul, Turkey.

Communications Biology
|August 21, 2025
PubMed

Insights

Dual-specificity tyrosine-phoshorylation-regulated kinases (DYRKs) regulate primary cilium assembly. DYRK3 and DYRK2 cooperate to control cilium length, stability, and morphology, offering therapeutic targets for related disorders.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Dual-specificity tyrosine-phoshorylation-regulated kinases (DYRKs) are vital enzymes involved in numerous cellular functions.
  • DYRK family members are implicated in cancers and developmental disorders, underscoring the need to understand their roles.
  • Primary cilia, crucial for cellular signaling, are regulated by DYRKs.

Purpose of the Study:

  • To identify DYRK3 interactors and elucidate its role in primary cilium biogenesis and maintenance.
  • To investigate the cooperative functions of DYRK family members in regulating cilium assembly.
  • To explore the therapeutic potential of targeting DYRK kinases in ciliopathies.

Main Methods:

  • Proximity interactome mapping to identify DYRK3-interacting proteins.
  • RNA interference (RNAi)-mediated depletion and pharmacological inhibition (GSK-626616) of DYRK kinases.
  • Phenotypic analysis of primary cilia length, stability, and morphology.
  • Co-depletion and rescue experiments to assess DYRK2 and DYRK3 cooperation.
  • Analysis of DYRKs' functional relationship with centriolar satellites and the intraflagellar transport (IFT) complex.

Main Results:

  • The proximity interactome of DYRK3 identified 178 interacting proteins, including those involved in primary cilium biogenesis.
  • Depletion or inhibition of DYRK3 and DYRK kinase activity led to primary cilium elongation, particularly in the distal segment.
  • DYRK2 and DYRK3 were found to cooperate in regulating cilium length.
  • DYRK inhibition induced ciliary defects, length fluctuations, and increased ectocytosis.
  • Functional relationships between DYRKs, centriolar satellites, and the IFT complex were uncovered.

Conclusions:

  • DYRK3 plays a significant role in primary cilium assembly and maintenance.
  • DYRK kinase activity is crucial for regulating primary cilium length, stability, and morphology.
  • DYRK2 and DYRK3 exhibit cooperative functions in controlling cilium length.
  • These findings provide insights into DYRK-mediated regulation of primary cilia and potential therapeutic strategies.

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