comparative proteomic analysis of lung lamellar bodies and lysosome-related organelles比较蛋白质组学分析肺片状的身体和lysosome-related细胞器.pdf

Comparative Proteomic Analysis of Lung Lamellar Bodies and Lysosome-Related Organelles 1 1 1 2 1 Ross Ridsdale , Cheng-Lun Na , Yan Xu , Kenneth D. Greis , Timothy Weaver * 1 Division of Pulmonary Biology, Cincinnati Children’s Hospital Medical Center, and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America, 2 Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America Abstract Pulmonary surfactant is a complex mixture of lipids and proteins that is essential for postnatal function. Surfactant is synthesized in alveolar type II cells and stored as multi-bilayer membranes in a specialized secretory lysosome-related organelle (LRO), known as the lamellar body (LB), prior to secretion into the alveolar airspaces. Few LB proteins have been identified and the mechanisms regulating formation and trafficking of this organelle are poorly understood. Lamellar bodies were isolated from rat lungs, separated into limiting membrane and core populations, fractionated by SDSand proteins identified by nanoLC-tandem mass spectrometry. In total 562 proteins were identified, significantly extending a previous study that identified 44 proteins in rat lung LB. The lung LB proteome reflects the dynamic interaction of this organelle with the biosynthetic, secretory and endocytic pathways of the type II epithelial cell. Comparison with other LRO proteomes indicated that 60% of LB proteins were detected in one or more of 8 other proteomes, confirming classification of the LB as a LRO. Remarkably the LB shared 37.8% of its proteins with the melanosome but only 9.9% with lamellar bodies from the skin.