title: Comparative proteomic analysis of lung lamellar bodies and lysosome-related organelles.
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 SDS-PAGE and 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. Of the 229 proteins not detected in other LRO proteomes, a subset of 34 proteins was enriched in lung relative to other tissues. Proteins with lipid-related functions comprised a significant proportion of the LB unique subset, consistent with the major function of this organelle in the organization, storage and secretion of surfactant lipid. The lung LB proteome will facilitate identification of molecular pathways involved in LB biogenesis, surfactant homeostasis and disease pathogenesis.
authors.affiliation: 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.
authors.forename: Ross
authors.initials: R
authors.lastname: Ridsdale
authors.forename: Cheng-Lun
authors.initials: CL
authors.lastname: Na
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Greis
authors.forename: Timothy
authors.initials: T
authors.lastname: Weaver
mesh_terms: D000818:Animals; D008168:Lung / Q000737:chemistry*; D008247:Lysosomes / Q000737:chemistry; D015388:Organelles / Q000737:chemistry; D011506:Proteins / Q000032:analysis*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D011650:Pulmonary Alveoli / Q000737:chemistry; D011663:Pulmonary Surfactants / Q000737:chemistry; D051381:Rats
chemical_list: D011506:Proteins; D020543:Proteome; D011663:Pulmonary Surfactants