What is it about?

Across species, Wnt signaling controls tissue polarity and cell fate. It has been suggested that Wnt-mediated multiprotein complexes like the "signalosome" and "destruction complex" represent biomolecular condensates. These non-membrane bound, specialized compartments shall ensure that physiological responses are carried out as intended. Biomolecular condensates have increasingly gained scientific interest. However, important research questions remain regarding their internal structure and physiological regulation. We used CRISPR/Cas9-mediated genome engineering to endogenously fuse a fluorescent protein to Dishevelled-2, a protein central to the Wnt signaling cascades. After functional validation of the fusion protein, we can use the fluorescent signal as a sourrogate for Dishevelled-2 in time-lapse imaging of living cells and for super-resolution microscopy.

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Why is it important?

Advanced imaging techniques provide insights into physiological Wnt signaling and protein activities. Single-molecule microscopy demonstrates close interactions of Wnt signaling components at and with the centrosome. This work uncovers the distinctive molecular architecture of endogenous Wnt signaling condensates at single-molecule resolution.

Perspectives

I work as a Clinician Scientist in basic research at the German Cancer Research Center (DKFZ, Heidelberg) and provide clinical care at the National Center for Tumor Diseases (NCT, Heidelberg). Wnt signaling governs various physiological processes. It is frequently found dysregulated in cancer. Clever ideas to specifically target dysregulated Wnt signaling in cancer are still lacking. In my opinion, better mechanistic understanding of the Wnt signaling cascades is necessary to specifically target dysregulated Wnt signaling therapeutically or use the knowledge for diagnostic purposes.

Antonia Schubert
Deutsches Krebsforschungszentrum

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This page is a summary of: Superresolution microscopy localizes endogenous Dvl2 to Wnt signaling-responsive biomolecular condensates, Proceedings of the National Academy of Sciences, July 2022, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2122476119.
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