Nucleation of the destruction complex on the centrosome accelerates degradation of ß-catenin and regulates Wnt signal transmission.
Proc Natl Acad Sci U S A
; 119(36): e2204688119, 2022 09 06.
Article
en En
| MEDLINE
| ID: mdl-36037369
ABSTRACT
Wnt signal transduction is controlled by the destruction complex (DC), a condensate comprising scaffold proteins and kinases that regulate ß-catenin stability. Overexpressed DC scaffolds undergo liquid-liquid phase separation (LLPS), but DC mesoscale organization at endogenous expression levels and its role in ß-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 ß-catenin by colocalizing DC components to a single reaction crucible. Enriching GSK3ß partitioning on the centrosome controls ß-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.
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Bases de datos:
MEDLINE
Asunto principal:
Centrosoma
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Beta Catenina
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Células Madre Embrionarias
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Vía de Señalización Wnt
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2022
Tipo del documento:
Article