Secretion of surfactant protein C, an integral membrane protein, requires the N-terminal propeptide

Proteolytic processing of surfactant protein C (SP-C) proprotein in multive sicular bodies of alveolar type II cells results in a 35-residue mature pep tide, consisting of a transmembrane domain and a 10-residue extramembrane d omain. SP-C mature peptide is stored in lamellar bodies (a lysosomal-like o rganelle) and secreted with surfactant phopholipids into the alveolar space . This study was designed to identify the peptide domain of SP-C required f or sorting and secretion of this integral membrane peptide. Deletion analys es in transiently transfected PC12 cells and isolated mouse type II cells s uggested the extramembrane domain of mature SP-C was cytosolic and sufficie nt for sorting to the regulated secretory pathway. Intratracheal injection of adenovirus encoding SP-C mature peptide resulted in secretion into the a lveolar space of wild type mice but not SP-C (-/-) mice, SP-C secretion in null mice was restored by the addition of the N-terminal propeptide, The cy tosolic domain, consisting of the N-terminal propeptide and extramembrane d omain of mature SP-C peptide, supported secretion of the transmembrane doma in of platelet-derived growth factor receptor, Collectively, these studies indicate that the N-terminal propeptide of SP-C is required for intracellul ar sorting and secretion of SP-C.