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Membrane 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...

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Detalles Bibliográficos
Autores principales: Kaur, Prameet, Lam, Vanessa Yuk Man, Mannava, Anirudh Gautam, Suresh, Jahnavi, Jenny, Andreas, Tolwinski, Nicholas S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537288/
https://www.ncbi.nlm.nih.gov/pubmed/28761148
http://dx.doi.org/10.1038/s41598-017-04414-0
Descripción
Sumario: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 constructs finding that both the DEP and PDZ domains are dispensable for canonical signaling only in membrane-tethered Dsh, but not in untethered/normal Dsh. These data lead to a signal activation model, where Arrow is required to localize Dsh to the membrane during canonical Wnt signaling placing Dsh downstream of Arrow.