Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling.
Ntourmas S, Sachs M, Paclíková P, Brückner M, Bryja V, Behrens J, Bernkopf DB (2024)
Publication Type: Journal article
Publication year: 2024
Journal
Book Volume: 13
DOI: 10.7554/eLife.96841
Abstract
Activation of the Wnt/β-catenin pathway crucially depends on the 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 in human cell lines, using a biochemical ultracentrifugation assay. We identify a low-complexity region (LCR4) in the C-terminus whose deletion and fusion decreased and increased the complexes, respectively. Notably, LCR4-induced complexes correlated with the formation of microscopically visible multimeric condensates. Adjacent to LCR4, we mapped a conserved domain (CD2) promoting condensates only. Molecularly, LCR4 and CD2 mediated DVL2 self-interaction via aggregating residues and phenylalanine stickers, respectively. Point mutations inactivating these interaction sites impaired Wnt pathway activation by DVL2. Our study discovers DVL2 complexes with functional importance for Wnt/β-catenin signaling. Moreover, we provide evidence that DVL2 condensates form in two steps by pre-oligomerization via high-affinity interaction sites, such as LCR4, and subsequent condensation via low-affinity interaction sites, such as CD2.
Involved external institutions
Czech Republic (CZ)How to cite
APA:
Ntourmas, S., Sachs, M., Paclíková, P., Brückner, M., Bryja, V., Behrens, J., & Bernkopf, D.B. (2024). Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling. eLife, 13. https://doi.org/10.7554/eLife.96841
MLA:
Ntourmas, Senem, et al. "Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling." eLife 13 (2024).
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