Fatty acid modification of Wnt1 and Wnt3a at serine is prerequisite for lipidation at cysteine and is essential for Wnt signalling
Abstract
Mammalian Wnt ligands contain two types of post-translational modification: the covalent attachment of fatty acids at two distinct positions, and the N-glycosylation of multiple asparagines. We examined how these modifications contribute to the secretion, extracellular movement and signaling activity of mouse Wnt1 and Wnt3a ligands.
We revealed that O-linked acylation of serine is required for the subsequent S-palmitoylation of cysteine. Interestingly, although double-acylation of Wnt1 was indispensable for signaling in mammalian cells, in Xenopus embryos the S-palmitoyl-deficient form retained the signaling activity.
In the case of Wnt3a, the functional duality of the attached acyls was less prominent, since the ligand lacking S-linked palmitate was still capable of signaling in various cellular contexts. Finally, we show that the signaling competency of both Wnt1 and Wnt3a is related to their ability to associate with the extracellular matrix.