Biosynthetic routing of pulmonary surfactant proteins in alveolar type II cells.
Surfactant proteins A, B, and C (SP-A, SP-B, and SP-C) are synthesized in alveolar type II cells. SP-B and SP-C are both synthesized as large precursor molecules that are proteolytically processed to their mature sizes. In a previous immunoelectron microscopic study, we showed that precursor SP-B is processed to its mature size in multivesicular bodies. In the present study, using a specific antibody against precursor SP-C, we demonstrate that precursor SP-C is present in the same intracellular compartments of the biosynthetic pathway, i.e., endoplasmic reticulum, Golgi complex, and multivesicular bodies, as precursor SP-B. Since mature SP-C is known to be present in multilamellar bodies, this suggests a biosynthetic routing and site of processing of this protein similar to those of SP-B. Double-labeling experiments using antibodies against SP-A, precursor SP-B, precursor SP-C, and an antibody against HA I, an adaptor protein involved in the budding of transport vesicles from the Golgi complex, showed that the different surfactant proteins traverse and exit the Golgi complex via the same route. The surfactant proteins do not exit the Golgi complex via HA I-positive coated buds or vesicles. These data are in accordance with the concept that SP-A, SP-B, and SP-C are transported together through the same biosynthetic pathway via multivesicular bodies to multilamellar bodies.
Voorhout
W F
WF
Laboratory of Veterinary Biochemistry, University of Utrecht, The Netherlands.
Weaver
T E
TE
Haagsman
H P
HP
Geuze
H J
HJ
Van Golde
L M
LM
D000911:Antibodies, Monoclonal; D001692:Biological Transport; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D006023:Glycoproteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000648:ultrastructure; D011499:Protein Processing, Post-Translational; D011510:Proteolipids / Q000096:biosynthesis / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000648:ultrastructure; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000096:biosynthesis / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants