Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5

Prameet Kaur, Vanessa Yuk Man Lam, Anirudh Gautam Mannava, Jahnavi Suresh, Andreas Jenny, Nicholas S. Tolwinski

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number6934
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General

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    Kaur, P., Lam, V. Y. M., Mannava, A. G., Suresh, J., Jenny, A., & Tolwinski, N. S. (2017). Membrane Targeting of Disheveled Can Bypass the Need for Arrow/LRP5. Scientific reports, 7(1), [6934]. https://doi.org/10.1038/s41598-017-04414-0