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XB-ART-55643
Cell Rep January 1, 2019; 26 (4): 875-883.e5.

Non-acylated Wnts Can Promote Signaling.

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


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.

PubMed ID: 30673610
PMC ID: PMC6429962
Article link: Cell Rep
Grant support: [+]
Genes referenced: fbrs myc nodal3.1 nodal3.2 rps3a sia1 szl wnt1 wnt3a wnt5a wnt8a
Antibodies: Tubb2b Ab8 Wnt1 Ab2 Wnt3a Ab2 Wnt5a Ab2


Article Images: [+] show captions
References [+] :
Alexandre, Patterning and growth control by membrane-tethered Wingless. 2014, Pubmed


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