Schubert et al., 2025, Image-based screens identify regulators of endogenous Dvl2 biomolecular condensates
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The paper this repository relates to is currently in submission.
This directory contains scripts and files supporting the publication:
Schubert et al., 2025, Image-based screens identify regulators of endogenous Dvl2 biomolecular condensates, Journal_TBA
Dishevelled (Dvl) proteins are essential transducers in Wnt signaling pathways, which have been implicated in development, stem cell maintenance, and human diseases such as cancer. Several studies have shown that Dvl proteins form dynamic biomolecular condensates. However, how cellular signals and cell states influence the formation of biomolecular condensates remains poorly understood. Here, we analyzed cells with endogenous Dvl2 condensates using image-based cell sorting in combination with phosphoproteomics and identified protein enrichment for Wnt/PCP signaling and the G2/M cell cycle transition. We then performed an image-based high-throughput screen to identify small molecule kinase inhibitors that affect Dvl2 liquid-liquid phase separation. Strikingly, CK1δ/ε inhibition blocked Dvl2 condensate formation. Its effect on Wnt signaling was modulated in genetic epistasis experiments with loss-of-function alleles of APC, Axin1, and MCC. Our study highlights the interplay between post-translational modifications and condensate dynamics, opening new avenues for research on their role in cellular signaling and disease intervention.
Should you encounter any issues or have any questions regarding code and data contained in this repository, please contact Antonia Schubert [email protected], Florian Heigwer [email protected] or Michael Boutros [email protected].