PUBLICATION
Non-acylated Wnts Can Promote Signaling
- Authors
- Speer, K.F., Sommer, A., Tajer, B., Mullins, M.C., Klein, P.S., Lemmon, M.A.
- ID
- ZDB-PUB-190124-7
- Date
- 2019
- Source
- Cell Reports 26: 875-883.e5 (Journal)
- Registered Authors
- Mullins, Mary C.
- Keywords
- Frizzled, Wnt, Xenopus laevis, acylation, lipid modification
- MeSH Terms
-
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Embryonic Development*
- Wnt Proteins/genetics
- Wnt Proteins/metabolism*
- Xenopus Proteins/genetics
- Xenopus Proteins/metabolism*
- HEK293 Cells
- Embryo, Nonmammalian/embryology*
- Humans
- Animals
- Wnt Signaling Pathway/physiology*
- Acylation
- Xenopus laevis
- Zebrafish/embryology*
- Zebrafish/genetics
- Frizzled Receptors/genetics
- Frizzled Receptors/metabolism
- PubMed
- 30673610 Full text @ Cell Rep.
Citation
Speer, K.F., Sommer, A., Tajer, B., Mullins, M.C., Klein, P.S., Lemmon, M.A. (2019) Non-acylated Wnts Can Promote Signaling. Cell Reports. 26:875-883.e5.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping