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

Dev Cell. 2006 Dec;11(6):791-801. doi: 10.1016/j.devcel.2006.10.003.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Embryo, Nonmammalian
  • Endoplasmic Reticulum / metabolism
  • Fatty Acids, Monounsaturated / metabolism*
  • Immunoblotting
  • Membrane Proteins / metabolism
  • Microinjections
  • Molecular Sequence Data
  • Nanotechnology
  • Protein Processing, Post-Translational
  • Protein Transport*
  • Sequence Homology, Amino Acid
  • Serine / chemistry
  • Serine / genetics
  • Serine / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Xenopus laevis / embryology
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism*


  • Fatty Acids, Monounsaturated
  • Membrane Proteins
  • Wnt Proteins
  • palmitoleic acid
  • Serine