Editors' ChoiceBiochemistry

Serine Acylation of Wnt

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Science's STKE  12 Dec 2006:
Vol. 2006, Issue 365, pp. tw415
DOI: 10.1126/stke.3652006tw415

Takada et al. provide evidence for a new type of protein acylation. Using transfected mouse L cells expressing Wnt-3a or Wnt-5a, the authors show that the proteins are acylated by incorporation of radiolabeled palmitic acid. This was not surprising, because Wnt had previously been reported to be palmitoylated on Cys77. What was surprising was that the acylation of Wnt-3a was not diminished by mutation of the Cys to alanine. The acylation site in Wnt-3a was mapped to Ser209 using deletion and point mutation constructs. Mass spectrometry analysis showed that Ser209 was modified by the addition of the monounsaturated lipid palmitoleic acid (C16:1). Porcupine is a putative O-acyltransferase, and in Drosophila porcupine is required for Wnt (called Wingless) secretion. Reduction of porcupine by small interfering RNA decreased the secretion of Wnt-3a and promoted the retention of the endoplasmic reticulum. Furthermore, the S209A mutant of Wnt-3a was also not secreted from the cells and was retained in the endoplasmic reticulum (ER). In the system used, Wnt-3a was predominantly in the ER because of the overexpression of the protein; therefore, to assess the effects of Ser209 acylation of transit through the biosynthetic pathway, the authors treated the cells with cycloheximide to block new protein synthesis. The functional consequences of acylation at Ser209 were assessed in a Xenopus development assay. Injection of embryos with Wnt-3a RNA causes ectopic axis formation; however, injection of the S209A mutant RNA did not cause any notable phenotype. These results open a new window into protein acylation with the addition of unsaturated lipids as modifiers of proteins (see Hausmann and Basler).

R. Takada, Y. Satomi, T. Kurata, N. Ueno, S. Norioka, H. Kondoh, T. Takao, S. Takada, Monounsaturated fatty acid modification of Wnt protein: Its role in Wnt secretion. Dev. Cell 11, 791-801 (2006). [PubMed]

G. Hausmann, K. Basler, Wnt lipid modifications: Not as saturated as we thought. Dev. Cell 11, 751-752 (2006). [PubMed]

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