Drosophila Wnt-1 Undergoes a Hydrophobic Modification and Is Targeted to Lipid Rafts, a Process That Requires Porcupine*

By Li-min Zhai, Deepti Chaturvedi, S. Cumberledge. 2004

260 citations recorded by the source corpus.

Wnt signaling pathways regulate many developmental responses; however, little is known about how Wnt ligands function on a biochemical level. Recent studies have shown that Wnt-3a is palmitoylated before secretion. Here we report that Drosophila Wnt-1 (Wingless) also undergoes a lipid modification. Lipidation occurs in the endoplasmic reticulum and is dependent on Porcupine, a putative O-acyltransferase. After modification, DWnt-1 partitions as a membrane-anchored protein and is sorted into lipid raft detergent-insoluble microdomains. Lipidation, raft targeting, and secretion can be blocked by the addition of 2-bromopalmitate, a competitive inhibitor of O-acyltransferase activity. Based on these results we propose a model whereby lipidation targets Wnt-1 to secretory vesicles that deliver the ligand to specialized microdomains at the cell surface where it can be packaged for secretion.

Subfields: Immunology, Molecular Biology

How researchers see this paper

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In Immunology

1. R. Nusse

In Molecular Biology

1. R. Nusse
2. C. Logan
3. S. Sarrazin
4. William C. Lamanna
5. R. Deschenes
6. J. Esko
7. M. Linder
8. K. Proffitt

Citations in the corpus

• Heparan sulfate proteoglycans. (2011, background): “The ability of glypicans to localize into lipid rafts may allow them to associate more directly with a number of morphogens, such as Hh and Wg, which are themselves lipidated (Rietveld et al. 1999; Zhai et al. 2004).”
• Wnt/beta-catenin signaling in development and disease. (2006, unknown): “Thus, porcupine and its worm homolog mom-1 are believed to encode the enzyme that is responsible for Wnt palmitoylation (Zhai et al., 2004).”
• The Wnt signaling pathway in development and disease. (2004, background): “Therefore, it is possible that por encodes an enzyme that catalyzes the transfer of palmitate onto Wnt. Consistent with this idea, Wingless, like Wnt3a, is also hydrophobic (Zhai et al. 2004).”
• Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion. (2006, background): “One important step regulating the extracellular transport of various secreted signal proteins, including Wnt, Hedgehog (Hh), and Spitz (Drosophila Transforming Growth Factor a), involves posttranslational modification with lipid moieties (Mann and Beachy, 2004; Miura et al., 2006; Nusse, 2003).”
• Precise Regulation of Porcupine Activity Is Required for Physiological Wnt Signaling (2012, background): “PORCN is a membrane-bound O-acyltransferase (MBOAT), and it catalyzes the palmitoylation of the serine corresponding to Ser-209 ofWNT3A (17, 18).”
• Wnt signaling and stem cell control (2008, background): “2007), whereas loss of porc decreases the hydrophobicity of Wg (Zhai et al. 2004).”
• Thematic review series: Lipid Posttranslational Modifications. Protein palmitoylation by a family of DHHC protein S-acyltransferases Published, JLR Papers in Press, April 1, 2006. (2006, background): “Porcupine is required for the modification of Wnt proteins (16).”