Drosophila wnt-1 undergoes a hydrophobic modification and is targeted to lipid rafts, a process that requires porcupine.
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.
Zhai
Linda
L
Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, Massachusetts 01003, USA.
Chaturvedi
Deepti
D
Cumberledge
Susan
S
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology; D019308:Palmitic Acid / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism; D051153:Wnt Proteins; D051155:Wnt1 Protein
D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D010168:Palmitates; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; C103067:por protein, Drosophila; C022776:2-bromopalmitate; D019308:Palmitic Acid