Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion.
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.
Takada
Ritsuko
R
Okazaki Institute for Integrative Biosciences, National Institutes of Natural Sciences, Okazaki, Aichi 444-8787, Japan.
Satomi
Yoshinori
Y
Kurata
Tomoko
T
Ueno
Naoto
N
Norioka
Shigemi
S
Kondoh
Hisato
H
Takao
Toshifumi
T
Takada
Shinji
S
D000215:Acylation; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D015151:Immunoblotting; D008565:Membrane Proteins / Q000378:metabolism; D008845:Microinjections; D008969:Molecular Sequence Data; D036103:Nanotechnology; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics / Q000378:metabolism*
D005229:Fatty Acids, Monounsaturated; D008565:Membrane Proteins; D051153:Wnt Proteins; C008757:palmitoleic acid; D012694:Serine