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eLife Assessment This valuable study contributes to the understanding of phase separation in Dishevelled (DVL) proteins, by investigating the endogenous complexes of DVL2 using ultracentrifugation and contrasting them with DVL1 and DVL3 behaviour and the functional validation of the DVL2 intrinsically disordered regions mediating the protein condensate. The study includes a solid characterisation of several overexpression constructs, including in KO cells.
Abstract Activation of the Wnt/beta-catenin pathway crucially depends on polymerization of dishevelled 2 (DVL2) into biomolecular condensates. However, given the low affinity of known DVL2 self-interaction sites and its low cellular concentration it is unclear how polymers can form. Here, we detect oligomeric DVL2 complexes at endogenous protein levels, using a biochemical ultracentrifugation assay.
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