Kinase activity of DYRK family members is required for regulating primary cilium length, stability and morphology
Abstract The dual-specificity tyrosine-phoshorylation-regulated kinase (DYRK) family are multifunctional enzymes crucial for diverse cellular processes, including signaling through the primary cilium. Their dysregulation has been implicated in various cancers and developmental disorders, highlightin...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08373-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Abstract The dual-specificity tyrosine-phoshorylation-regulated kinase (DYRK) family are multifunctional enzymes crucial for diverse cellular processes, including signaling through the primary cilium. Their dysregulation has been implicated in various cancers and developmental disorders, highlighting the need to define their interactors and cellular functions to inform targeted therapeutics. In this study, we generate the proximity interactome of DYRK3, identifying 178 proteins involved in a range of cellular processes, including primary cilium biogenesis. We then investigate the specific role of DYRK3 and its cooperation with other DYRK family members in cilium assembly and maintenance. RNAi-mediated depletion of DYRK3 and pharmacological inhibition of DYRK kinase activity using GSK-626616 (GSK) lead to elongation of the cilium, particularly its distal segment. GSK treatment also induces ciliary defects, length fluctuations, and increased ectocytosis. Co-depletion and phenotypic rescue experiments reveal that DYRK2 and DYRK3 cooperate in regulating cilium length. Moreover, inhibiting or depleting known cilium length regulators, or quantifying their ciliary levels in GSK-treated cells, reveal functional relationships of DYRKs to centriolar satellites and the IFT complex. Collectively, our findings uncover regulatory roles for DYRK3 and DYRK kinase activity in the assembly and maintenance of primary cilium with proper length, stability, and morphology. |
|---|---|
| ISSN: | 2399-3642 |