Pathway to lamellar bodies for surfactant protein A
- 1 July 2010
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Lung Cellular and Molecular Physiology
- Vol. 299 (1), L51-L58
- https://doi.org/10.1152/ajplung.00066.2010
Abstract
Alveolar surfactant protein A (SP-A) is endocytosed by type II epithelial cells through clathrin-dependent uptake and targeted to lamellar bodies for resecretion. However, the mechanism for secretion of newly synthesized SP-A, whether regulated exocytosis of lamellar bodies or constitutive secretion, is unresolved. If it is the latter, lamellar body SP-A would represent endocytosed protein. Amantadine, an inhibitor of clathrin-coated vesicle budding, was used to evaluate the role of endocytosis in accumulation of SP-A in lamellar bodies. In isolated rat lungs, amantadine (10 mM) inhibited uptake of endotracheally instilled35S-labeled biosynthesized surfactant proteins by >80%. To study trafficking of newly synthesized SP-A, lungs were perfused for up to 6 h with [35S]methionine, and surfactant was isolated from lung lavage fluid and lamellar bodies were isolated from lung homogenate. With control lungs, the mean specific activity of [35S]SP-A (disintegrations per minute per microgram of SP-A) increased linearly with time of perfusion: it was significantly higher in isolated lamellar bodies than in surfactant and was increased in both compartments by 50–60% in the presence of 0.1 mM 8-bromo-cAMP. These results suggest a precursor-product relationship between lamellar body and extracellular [35S]SP-A. Specific activities in both compartments were unaffected by addition of amantadine (10 mM) to the lung perfusate, indicating that uptake from the alveolar space was not responsible for the increase in lamellar body [35S]SP-A. Thus the pathway for secretion of newly synthesized SP-A is by transfer from the site of synthesis to the storage/secretory organelle prior to lamellar body exocytosis.Keywords
This publication has 44 references indexed in Scilit:
- Role of P63 (CKAP4) in binding of surfactant protein-A to type II pneumocytesAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2008
- Distribution of intracellular and secreted surfactant during postnatal rat lung developmentPediatric Pulmonology, 2007
- Identification and characterization of p63 (CKAP4/ERGIC-63/CLIMP-63), a surfactant protein A binding protein, on type II pneumocytesAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2006
- Interaction of Surfactant Protein A with Peroxiredoxin 6 Regulates Phospholipase A2 ActivityOnline Journal of Public Health Informatics, 2006
- Pulmonary surfactant transport in alveolar type II cellsRespirology, 2006
- Pathways for clearance of surfactant protein A from the lungAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2005
- The Role of Pulmonary Collectin N-terminal Domains in Surfactant Structure, Function, and Homeostasis in VivoOnline Journal of Public Health Informatics, 2002
- Synthesis of surfactant components by cultured type II cells from human lungBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1988
- Isolation and characterization of differentiated alveolar type II cells from fetal human lungBiochimica et Biophysica Acta (BBA) - General Subjects, 1986
- Isolation of lamellar bodies from rat granular pneumocytes in primary cultureBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1983