title: Biologically active APRIL is secreted following intracellular processing in the Golgi apparatus by furin convertase.
abstract: Tumor necrosis factor (TNF) ligand family members are synthesized as transmembrane proteins, and cleavage of the membrane-anchored proteins from the cell surface is frequently observed. The TNF-related ligands APRIL and BLyS and their cognate receptors BCMA/TACI form a two ligand/two receptor system that has been shown to participate in B- and T-cell stimulation. In contrast to BLyS, which is known to be cleaved from the cell surface, we found that APRIL is processed intracellularly by furin convertase. Blockage of protein transport from the endoplasmic reticulum to the Golgi apparatus by Brefeldin A treatment abrogated APRIL processing, whereas monensin, an inhibitor of post-Golgi transport, did not interfere with cleavage of APRIL, but blocked secretion of processed APRIL. Thus, APRIL shows a unique maturation pathway among the TNF ligand family members, as it not detectable as a membrane-anchored protein at the cell surface, but is processed in the Golgi apparatus prior to its secretion.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, UAM Campus de Cantoblanco, E-28049 Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: López-Fraga
authors.forename: R
authors.initials: R
authors.lastname: Fernández
authors.forename: J P
authors.initials: JP
authors.lastname: Albar
authors.forename: M
authors.initials: M
authors.lastname: Hahne
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D001692:Biological Transport; D015153:Blotting, Western; D020126:Brefeldin A / Q000494:pharmacology; D002455:Cell Division; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D045683:Furin; D006056:Golgi Apparatus / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D013381:Subtilisins / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D008024:Ligands; D008565:Membrane Proteins; D011994:Recombinant Proteins; C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha; D020126:Brefeldin A; D013381:Subtilisins; D045683:Furin