Endocytosed SP-A and surfactant lipids are sorted to different organelles in rat type II pneumocytes.
Intracellular transport of endocytosed surfactant protein A (SP-A) and lipid was investigated in isolated rat type II cells. After internalization, SP-A and lipid are taken up via the coated-pit pathway and reside in a common compartment, positive for the early endosomal marker EEA1 but negative for the lamellar body marker 3C9. SP-A then recycles rapidly to the cell surface via Rab4-associated recycling vesicles. Internalized lipid is transported toward a Rab7-, CD63-, 3C9-positive compartment, i.e., lamellar bodies. Inhibition of calmodulin led to inhibition of uptake and transport out of the EEA1-positive endosome and thus of resecretion of both components. Inhibition of intravesicular acidification (bafilomycin A1) led to decreased uptake of both surfactant components. It inhibited transport out of early endosomes for lipid only, not for SP-A. We conclude that in type II cells, endocytosed SP-A and lipid are transported toward a common early endosomal compartment. Thereafter, both components dissociate. SP-A is rapidly recycled to the cell surface and does not enter classic lamellar bodies. Lipid is transported toward lamellar bodies.
Wissel
H
H
Clinic of Neonatology, University Children's Hospital Charité, Humboldt-University Berlin, 10098 Berlin, Germany.
Lehfeldt
A
A
Klein
P
P
Müller
T
T
Stevens
P A
PA
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D050356:Lipid Metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D018942:Macrolides; D008297:Male; D015388:Organelles / Q000378:metabolism*; D011510:Proteolipids / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D012756:Sheep; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D018942:Macrolides; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D013449:Sulfonamides; C017967:W 7; C040929:bafilomycin A1; D000255:Adenosine Triphosphate; D013755:Tetradecanoylphorbol Acetate