Class-Wide Analysis of Frizzled-Dishevelled Interactions Using BRET Biosensors Reveals Functional Differences among Receptor Paralogs.

ABSTRACT: Wingless/Int-1 (WNT) signaling is mediated by WNT binding to 10 Frizzleds (FZD_1-10), which propagate the signal inside the cell by interacting with different transducers, most prominently the phosphoprotein Dishevelled (DVL). Despite recent progress, questions about WNT/FZD selectivity and paralog-dependent differences in the FZD/DVL interaction remain unanswered. Here, we present a class-wide analysis of the FZD/DVL interaction using the DEP domain of DVL as a proxy in bioluminescence resonance energy transfer (BRET) techniques. Most FZDs engage in a constitutive high-affinity interaction with DEP. Stimulation of unimolecular FZD/DEP BRET sensors with different ligands revealed that most paralogs are dynamic in the FZD/DEP interface, showing distinct profiles in terms of ligand

SUBMITTER: Gratz L 

PROVIDER: S-EPMC11443525 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature