title: PAPST1 regulates sulfation of heparan sulfate proteoglycans in epithelial MDCK II cells.
abstract: Proteoglycan (PG) sulfation depends on activated nucleotide sulfate, 3'-phosphoadenosine-5'-phosphosulfate (PAPS). Transporters in the Golgi membrane translocate PAPS from the cytoplasm into the organelle lumen where PG sulfation occurs. Silencing of PAPS transporter (PAPST) 1 in epithelial MDCK cells reduced PAPS uptake into Golgi vesicles. Surprisingly, at the same time sulfation of heparan sulfate (HS) was stimulated. The effect was pathway specific in polarized epithelial cells. Basolaterally secreted proteoglycans (PGs) displayed an altered HS sulfation pattern and increased growth factor binding capacity. In contrast, the sulfation pattern of apically secreted PGs was unchanged while the secretion was reduced. Regulation of PAPST1 allows epithelial cells to prioritize between PG sulfation in the apical and basolateral secretory routes at the level of the Golgi apparatus. This provides sulfation patterns that ensure PG functions at the extracellular level, such as growth factor binding.
authors.affiliation: Department of Biosciences, University of Oslo, PO Box 1066, 0316 Oslo, Norway gunnar.dick@ibv.uio.no.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Dick
authors.affiliation: Department of Biosciences, University of Oslo, PO Box 1066, 0316 Oslo, Norway.
authors.forename: Linn Kristin
authors.initials: LK
authors.lastname: Akslen-Hoel
authors.affiliation: Department of Biosciences, University of Oslo, PO Box 1066, 0316 Oslo, Norway.
authors.forename: Frøy
authors.initials: F
authors.lastname: Grøndahl
authors.affiliation: Department of Biosciences, University of Oslo, PO Box 1066, 0316 Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kjos
authors.affiliation: Department of Experimental Medical Science, Lund University, 221 00 Lund, Sweden.
authors.forename: Marco
authors.initials: M
authors.lastname: Maccarana
authors.affiliation: Department of Biosciences, University of Oslo, PO Box 1066, 0316 Oslo, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Prydz
mesh_terms: D000818:Animals; D001692:Biological Transport; D016764:Cell Polarity; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000378:metabolism*; D004285:Dogs; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010724:Phosphoadenosine Phosphosulfate / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D002809:Chondroitin Sulfates; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D036341:Intercellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D010724:Phosphoadenosine Phosphosulfate; D034741:RNA, Small Interfering
keywords: Golgi; HS; PAPS; glycosaminoglycan; sulfation