ABCA3 as a lipid transporter in pulmonary surfactant biogenesis
ABCA3 as a lipid transporter in pulmonary surfactant biogenesis
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DOI：
10.1074/jbc.m611767200
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发表时间：
2007-03-30
影响因子：
4.8
通讯作者：
Inagaki, Nobuya
中科院分区：
文献类型：
--
作者：
Ban, Nobuhiro;Matsumura, Yoshihiro;Inagaki, Nobuya
ABCA3蛋白主要表达在肺泡11型细胞板层小体的限制膜上，ABCA3基因突变可导致新生儿致死性呼吸窘迫。为了研究ABCA3蛋白的功能，我们通过靶向Abca3建立了Abca3缺陷小鼠。FullTerm Abca3(-/-)新生幼崽出生后一小时内死于急性呼吸衰竭。超微结构分析显示Abca3(-/-)肺泡II型细胞内有异常致密的板层体样细胞器，无正常板层小体。肺间质脂质的薄层色谱和电喷雾电离质谱分析表明，Abca3(-/-)肺组织中含有丰富的棕榈酸的磷脂酰胆碱和磷脂酰甘油。这些发现表明，ABCA3在肺表面活性物质脂代谢和板层小体生物发生中起重要作用，可能是通过转运这些脂质作为底物。
ABCA3 protein is expressed predominantly at the limiting membrane of the lamellar bodies in alveolar type 11 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. Fullterm 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.