Non-acylated Wnts Can Promote Signaling.

Abstract:

:Wnts are a family of 19 extracellular ligands that regulate cell fate, proliferation, and migration during metazoan embryogenesis and throughout adulthood. Wnts are acylated post-translationally at a conserved serine and bind the extracellular cysteine-rich domain (CRD) of Frizzled (FZD) seven-pass transmembrane receptors. Although crystal structures suggest that acylation is essential for Wnt binding to FZDs, we show here that several Wnts can promote signaling in Xenopus laevis and Danio rerio embryos, as well as in an in vitro cell culture model, without acylation. The non-acylated Wnts are expressed at levels similar to wild-type counterparts and retain CRD binding. By contrast, we find that certain other Wnts do require acylation for biological activity in Xenopus embryos, although not necessarily for FZD binding. Our data argue that acylation dependence of Wnt activity is context specific. They further suggest that acylation may underlie aspects of ligand-receptor selectivity and/or control other aspects of Wnt function.

journal_name

Cell Rep

journal_title

Cell reports

authors

Speer KF,Sommer A,Tajer B,Mullins MC,Klein PS,Lemmon MA

doi

10.1016/j.celrep.2018.12.104

subject

Has Abstract

pub_date

2019-01-22 00:00:00

pages

875-883.e5

issue

4

issn

2211-1247

pii

S2211-1247(18)32079-5

journal_volume

26

pub_type

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