title: The surfactant lipid transporter ABCA3 is N-terminally cleaved inside LAMP3-positive vesicles.
abstract: ABCA3 mutations cause fatal surfactant deficiency and interstitial lung disease. ABCA3 protein is a lipid transporter indispensible for surfactant biogenesis and storage in lamellar bodies (LB). The protein folds in endoplasmic reticulum and is glycosylated in Golgi en route to the membrane of mature LB and their precursor multivesicular bodies (MVB). In immunoblots, C-terminally labeled ABCA3 appears as two protein bands of 150 and 190 kDa. Using N- and C-terminal protein tags and hindering ABCA3 processing we show that the 150 kDa protein represents the mature ABCA3 whose N-terminus is cleaved by a cysteine protease inside MVB/LB.
authors.affiliation: Pediatric Pneumology, Dr. von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Engelbrecht
authors.forename: Eva
authors.initials: E
authors.lastname: Kaltenborn
authors.forename: Matthias
authors.initials: M
authors.lastname: Griese
authors.forename: Suncana
authors.initials: S
authors.lastname: Kern
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051907:Lysosomal Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D057146:Multivesicular Bodies / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010436:Pepstatins / Q000494:pharmacology; D017510:Protein Folding; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D059666:Lysosomal-Associated Membrane Protein 3
chemical_list: D018528:ATP-Binding Cassette Transporters; D015853:Cysteine Proteinase Inhibitors; D007930:Leucine; D008164:Luminescent Proteins; D051907:Lysosomal Membrane Proteins; D009363:Neoplasm Proteins; D010436:Pepstatins; C441524:ABCA3 protein, human; C114233:LAMP3 protein, human; D059666:Lysosomal-Associated Membrane Protein 3; C024974:E 64; C031375:pepstatin