biostudies-literatureKaur PNIGMS NIH HHS6934https://www.ebi.ac.uk/biostudies/studies/S-EPMC5537288biostudies-literatureUnknown7(1)The highly conserved Wnt signaling pathway regulates cell proliferation and differentiation in vertebrates and invertebrates. Upon binding of a Wnt ligand to a receptor of the Fz family, Disheveled (Dsh/Dvl) transduces the signal during canonical and non-canonical Wnt signaling. The specific details of how this process occurs have proven difficult to study, especially as Dsh appears to function as a switch between different branches of Wnt signaling. Here we focus on the membrane-proximal events that occur once Dsh is recruited to the membrane. We show that membrane-tethering of the Dsh protein is sufficient to induce canonical Wnt signaling activation even in the absence of the Wnt co-receptor Arrow/LRP5/6. We map the protein domains required for pathway activation in membrane tethered coScientific reportsMembrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5.PMC5537288R01 GM115646Tolwinski NSJenny AKaur PMannava AGSuresh JLam VYMfalseMembrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5.The highly conserved Wnt signaling pathway regulates cell proliferation and differentiation in vertebrates and invertebrates. Upon binding of a Wnt ligand to a receptor of the Fz family, Disheveled (Dsh/Dvl) transduces the signal during canonical and non-canonical Wnt signaling. The specific details of how this process occurs have proven difficult to study, especially as Dsh appears to function as a switch between different branches of Wnt signaling. Here we focus on the membrane-proximal events that occur once Dsh is recruited to the membrane. We show that membrane-tethering of the Dsh protein is sufficient to induce canonical Wnt signaling activation even in the absence of the Wnt co-receptor Arrow/LRP5/6. We map the protein domains required for pathway activation in membrane tethered co2017-01-01T00:00:00Z2017 Jul2025-06-01T02:53:16.901Z2025-06-01T02:53:16.901ZS-EPMC55372882876114810.1038/s41598-017-04414-0