[PDF][PDF] Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion

R Takada, Y Satomi, T Kurata, N Ueno, S Norioka… - Developmental cell, 2006 - cell.com
R Takada, Y Satomi, T Kurata, N Ueno, S Norioka, H Kondoh, T Takao, S Takada
Developmental cell, 2006cell.com
The secretion and extracellular transport of Wnt protein are thought to be well-regulated
processes. Wnt is known to be acylated with palmitic acid at a conserved cysteine residue
(Cys77 in murine Wnt-3a), and this residue appears to be required for the control of
extracellular transport. Here, we show that murine Wnt-3a is also acylated at a conserved
serine residue (Ser209). Of note, we demonstrated that this residue is modified with a
monounsaturated fatty acid, palmitoleic acid. Wnt-3a defective in acylation at Ser209 is not …
Summary
The secretion and extracellular transport of Wnt protein are thought to be well-regulated processes. Wnt is known to be acylated with palmitic acid at a conserved cysteine residue (Cys77 in murine Wnt-3a), and this residue appears to be required for the control of extracellular transport. Here, we show that murine Wnt-3a is also acylated at a conserved serine residue (Ser209). Of note, we demonstrated that this residue is modified with a monounsaturated fatty acid, palmitoleic acid. Wnt-3a defective in acylation at Ser209 is not secreted from cells in culture or in Xenopus embryos, but it is retained in the endoplasmic reticulum (ER). Furthermore, Porcupine, a protein with structural similarities to membrane-bound O-acyltransferases, is required for Ser209-dependent acylation, as well as for Wnt-3a transport from the ER for secretion. These results strongly suggest that Wnt protein requires a particular lipid modification for proper intracellular transport during the secretory process.
cell.com