title: Dynamic palmitoylation of lymphoma proprotein convertase prolongs its half-life, but is not essential for trans-Golgi network localization.
abstract: Proprotein convertases are responsible for the endoproteolytic activation of proproteins in the secretory pathway. The most recently discovered member of this family, lymphoma proprotein convertase (LPC), is a type-I transmembrane protein. Previously, we have demonstrated that its cytoplasmic tail is palmitoylated. In this study, we have identified the two most proximal cysteine residues in the cytoplasmic tail as palmitoylation sites. Substitution of either cysteine residue by alanine interfered with palmitoylation of the other. Palmitoylation of LPC was found to be sensitive to the protein palmitoyltransferase inhibitor tunicamycin but not cerulenin. It was also insensitive to the drugs brefeldin A, monensin and cycloheximide, indicating that the modification occurs in a late exocytic or endocytic compartment. Turnover of palmitoylated LPC is significantly faster (t(1/2) approximately 50 min) than that of the LPC polypeptide backbone (t(1/2) approximately 3 h), suggesting that palmitoylation is reversible. Abrogation of palmitoylation reduced the half-life of the LPC protein, but did not affect steady-state localization of LPC in the trans-Golgi network. Finally, LPC could not be detected in detergent-resistant membrane rafts. Taken together, these results suggest that dynamic palmitoylation of LPC is important for stability, but does not function as a dominant trafficking signal.
authors: Laboratory for Molecular Oncology, Center for Human Genetics, University of Leuven and Flanders Interuniversity Institute for Biotechnology, Herestraat 49, 3000 Leuven, Belgium.
authors: J W
authors: JW
authors: van de Loo
authors: M
authors: M
authors: Teuchert
authors: I
authors: I
authors: Pauli
authors: E
authors: E
authors: Plets
authors: W J
authors: WJ
authors: Van de Ven
authors: J W
authors: JW
authors: Creemers
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D020126:Brefeldin A / Q000494:pharmacology; D002569:Cerulenin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004795:Enzyme Stability / Q000187:drug effects; D005089:Exocytosis; D019084:Fluorescent Antibody Technique, Indirect; D006207:Half-Life; D008223:Lymphoma / Q000201:enzymology*; D021962:Membrane Microdomains / Q000737:chemistry / Q000187:drug effects; D008985:Monensin / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D019308:Palmitic Acid / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021382:Protein Sorting Signals / Q000502:physiology; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D013381:Subtilisins; D014415:Tunicamycin / Q000494:pharmacology; D021601:trans-Golgi Network / Q000187:drug effects / Q000201:enzymology*
chemical_list: D021382:Protein Sorting Signals; D014415:Tunicamycin; D002569:Cerulenin; D020126:Brefeldin A; D019308:Palmitic Acid; D008985:Monensin; D003513:Cycloheximide; C099101:PCSK7 protein, human; D012697:Serine Endopeptidases; D013381:Subtilisins; D003545:Cysteine