Title : Fatty acid modification of
Wnt1 and
Wnt3a at
serine is
prerequisite for lipidation at
cysteine and is essential for
Wnt signalling
Abstract :
- The Wnt family of proteins is a group of extracellular signalling molecules that regulate cell-fate decisions in developing and adult tissues
- It is presumed that all 19 mammalian Wnt family members 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 signalling activity of mouse Wnt1 and Wnt3a ligands
- We revealed that O-linked acylation of serine is required for the subsequent S-palmitoylation of cysteine
- As such, mutant proteins that lack the crucial serine residue are not lipidated
- Interestingly, although double-acylation of Wnt1 was indispensable for signalling in mammalian cells, in Xenopus embryos the S-palmitoyl-deficient form retained the signalling 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 signalling in various cellular contexts
- Finally , we show that the signalling competency of both Wnt1 and Wnt3a is related to their ability to associate with the extracellular matrix