title: Porcupine is not required for the production of the majority of Wnts from primary human astrocytes and CD8+ T cells.
abstract: Wnts are small secreted glycoproteins that are highly conserved among species. To date, 19 Wnts have been described, which initiate a signal transduction cascade that is either β-catenin dependent or independent, culminating in the regulation of hundreds of target genes. Extracellular release of Wnts is dependent on lipidation of Wnts by porcupine, a membrane-bound-O-acyltransferase protein in the endoplasmic reticulum. Studies demonstrating the requirement of porcupine for Wnts production are based on cell line and non-human primary cells. We evaluated the requirement for porcupine for Wnts production in human primary astrocytes and CD8+ T cells. Using IWP-2, an inhibitor of porcupine, or siRNA targeting porcupine, we demonstrate that porcupine is not required for the release of Wnt 1, 3, 5b, 6,7a, 10b, and 16a. While IWP had no effect on Wnt 2b release, knockdown of porcupine by siRNA reduced Wnt 2b release by 60%. These data indicate that porcupine-mediated production of Wnts is context dependent and is not required for all Wnts production, suggesting that alternative mechanisms exist for Wnts production.
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Maureen H
authors.initials: MH
authors.lastname: Richards
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Melanie S
authors.initials: MS
authors.lastname: Seaton
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Jennilee
authors.initials: J
authors.lastname: Wallace
authors.affiliation: Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Lena
authors.initials: L
authors.lastname: Al-Harthi
mesh_terms: D000217:Acyltransferases; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051153:Wnt Proteins / Q000096:biosynthesis*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D000217:Acyltransferases; C491188:PORCN protein, human