title: ABCA3 as a lipid transporter in pulmonary surfactant biogenesis.
abstract: ABCA3 protein is expressed predominantly at the limiting membrane of the lamellar bodies in alveolar type II cells, and mutations in the ABCA3 gene cause lethal respiratory distress in newborn infants. To investigate the function of ABCA3 protein, we generated Abca3-deficient mice by targeting Abca3. Full-term Abca3(-/-) newborn pups died within an hour after birth because of acute respiratory failure. Ultrastructural analysis revealed abnormally dense lamellar body-like organelles and no normal lamellar bodies in Abca3(-/-) alveolar type II cells. TLC and electrospray ionization mass spectrometry analyses of lipids in the pulmonary interstitium showed that phosphatidylcholine and phosphatidylglycerol, which contain palmitic acid and are abundant in normal surfactant lipids, were dramatically decreased in Abca3(-/-) lung. These findings indicate that ABCA3 plays an essential role in pulmonary surfactant lipid metabolism and lamellar body biogenesis, probably by transporting these lipids as substrates.
authors.affiliation: Department of Physiology, Akita University School of Medicine, and Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Agency (JST), Akita 010-8543, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ban
authors.affiliation: Department of Physiology, Akita University School of Medicine, and Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Agency (JST), Akita 010-8543, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsumura
authors.affiliation: Department of Physiology, Akita University School of Medicine, and Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Agency (JST), Akita 010-8543, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Takanezawa
authors.affiliation: Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, and CREST-JST, Kyoto 606-8507, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.affiliation: Department of Physiology, Akita University School of Medicine, and Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Agency (JST), Akita 010-8543, Japan; Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, and CREST-JST, Kyoto 606-8507, Japan. Electronic address: inagaki@metab.kuhp.kyoto-u.ac.jp.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D050356:Lipid Metabolism / Q000502:physiology*; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011663:Pulmonary Surfactants / Q000378:metabolism*; D013379:Substrate Specificity / Q000502:physiology
chemical_list: D018528:ATP-Binding Cassette Transporters; C512026:Abca3 protein, mouse; D011663:Pulmonary Surfactants