Involvement of napsin A in the C- and N-terminal processing of surfactant protein B in type-II pneumocytes of the human lung.

Brasch F, Ochs M, Kahne T, Guttentag S, Schauer-Vukasinovic V, Derrick M, Johnen G, Kapp N, Muller KM, Richter J, Giller T, Hawgood S, Buhling F
J Biol Chem. 2003 278 (49): 49006-14

PMID: 13129928 · DOI:10.1074/jbc.M306844200

Surfactant protein B (SP-B) is a critical component of pulmonary surfactant, and a deficiency of active SP-B results in fatal respiratory failure. SP-B is synthesized by type-II pneumocytes as a 42-kDa propeptide (proSP-B), which is posttranslationally processed to an 8-kDa surface-active protein. Napsin A is an aspartic protease expressed in type-II pneumocytes. To characterize the role of napsin A in the processing of proSP-B, we colocalized napsin A and precursors of SP-B as well as SP-B in the Golgi complex, multivesicular, composite, and lamellar bodies of type-II pneumocytes in human lungs using immunogold labeling. Furthermore, we measured aspartic protease activity in isolated lamellar bodies as well as isolated human type-II pneumocytes and studied the cleavage of proSP-B by napsin A and isolated lamellar bodies in vitro. Both, napsin A and isolated lamellar bodies cleaved proSP-B and generated three identical processing products. Processing of proSP-B by isolated lamellar bodies was completely inhibited by an aspartic protease inhibitor. Sequence analysis of proSP-B processing products revealed several cleavage sites in the N- and C-terminal propeptides as well as one in the mature peptide. Two of the four processing products generated in vitro were also detected in type-II pneumocytes. In conclusion, our results show that napsin A is involved in the N- and C-terminal processing of proSP-B in type-II pneumocytes.

MeSH Terms (10)

Amino Acid Sequence Aspartic Acid Endopeptidases Humans Immunohistochemistry Lung Microscopy, Immunoelectron Molecular Sequence Data Protein Processing, Post-Translational Pulmonary Surfactant-Associated Protein B Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

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