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.
- MeSH
- buněčné linie MeSH
- cystein metabolismus MeSH
- embryonální vývoj MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- lipoylace MeSH
- molekulární sekvence - údaje MeSH
- mutace MeSH
- myši MeSH
- protein Wnt1 genetika metabolismus MeSH
- protein Wnt3 MeSH
- protein Wnt3A MeSH
- proteiny Wnt genetika metabolismus MeSH
- proteiny Xenopus MeSH
- sekvence aminokyselin MeSH
- serin metabolismus MeSH
- substituce aminokyselin MeSH
- Xenopus embryologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
