Monounsaturated Fatty Acid Modification of Wnt Protein: Its Role in Wnt Secretion

• DOI: 10.1016/j.devcel.2006.10.003
• Publication Date: 2006-12-05T12:11:14Z
• Authors: Ritsuko Takada; Yoshinori Satomi; Tomoko Kurata; Naoto Ueno; Shigemi Norioka; Hisato Kondoh; Toshifumi Takao; Shinji Takada
• Keywords: 0301 basic medicine; Embryo, Nonmammalian; Microinjections; Sequence Homology, Amino Acid; Acylation; Immunoblotting; Molecular Sequence Data; Membrane Proteins; Endoplasmic Reticulum; Fatty Acids, Monounsaturated; Wnt Proteins; Protein Transport; Xenopus laevis; 03 medical and health sciences; SIGNALING; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Serine; Animals; Nanotechnology; CELLBIO; Amino Acid Sequence; Protein Processing, Post-Translational; Cells, Cultured; Developmental Biology

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.