USF-LVHN SELECT
Nucleation of the destruction complex on the centrosome accelerates degradation of β-catenin and regulates Wnt signal transmission.
Publication/Presentation Date
9-6-2022
Abstract
Wnt signal transduction is controlled by the destruction complex (DC), a condensate comprising scaffold proteins and kinases that regulate β-catenin stability. Overexpressed DC scaffolds undergo liquid-liquid phase separation (LLPS), but DC mesoscale organization at endogenous expression levels and its role in β-catenin processing were previously unknown. Here, we find that DC LLPS is nucleated by the centrosome. Through a combination of CRISPR-engineered custom fluorescent tags, finite element simulations, and optogenetic tools that allow for manipulation of DC concentration and multivalency, we find that centrosomal nucleation drives processing of β-catenin by colocalizing DC components to a single reaction crucible. Enriching GSK3β partitioning on the centrosome controls β-catenin processing and prevents Wnt-driven embryonic stem cell differentiation to mesoderm. Our findings demonstrate the role of nucleators in controlling biomolecular condensates and suggest tight integration between Wnt signal transduction and the cell cycle.
Volume
119
Issue
36
First Page
2204688119
Last Page
2204688119
ISSN
1091-6490
Published In/Presented At
Lach, R. S., Qiu, C., Kajbaf, E. Z., Baxter, N., Han, D., Wang, A., Lock, H., Chirikian, O., Pruitt, B., & Wilson, M. Z. (2022). Nucleation of the destruction complex on the centrosome accelerates degradation of β-catenin and regulates Wnt signal transmission. Proceedings of the National Academy of Sciences of the United States of America, 119(36), e2204688119. https://doi.org/10.1073/pnas.2204688119
Disciplines
Medical Education | Medicine and Health Sciences
PubMedID
36037369
Department(s)
USF-LVHN SELECT Program, USF-LVHN SELECT Program Students
Document Type
Article