Secretion of surfactant protein C, an integral membrane protein, requires the N-terminal propeptide.
Proteolytic processing of surfactant protein C (SP-C) proprotein in multivesicular bodies of alveolar type II cells results in a 35-residue mature peptide, consisting of a transmembrane domain and a 10-residue extramembrane domain. SP-C mature peptide is stored in lamellar bodies (a lysosomal-like organelle) and secreted with surfactant phospholipids into the alveolar space. This study was designed to identify the peptide domain of SP-C required for sorting and secretion of this integral membrane peptide. Deletion analyses in transiently transfected PC12 cells and isolated mouse type II cells suggested the extramembrane domain of mature SP-C was cytosolic and sufficient for sorting to the regulated secretory pathway. Intratracheal injection of adenovirus encoding SP-C mature peptide resulted in secretion into the alveolar 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 cytosolic domain, consisting of the N- terminal propeptide and extramembrane domain of mature SP-C peptide, supported secretion of the transmembrane domain of platelet-derived growth factor receptor. Collectively, these studies indicate that the N-terminal propeptide of SP-C is required for intracellular sorting and secretion of SP-C.
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
J J
JJ
Conkright
J P
JP
Bridges
C L
CL
Na
W F
WF
Voorhout
B
B
Trapnell
S W
SW
Glasser
T E
TE
Weaver
D000595:Amino Acid Sequence; D000818:Animals; D004705:Endocytosis; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D016716:PC12 Cells; D011510:Proteolipids / Q000737:chemistry / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000378:metabolism*; D051381:Rats
D008565:Membrane Proteins; D011510:Proteolipids; D011663:Pulmonary Surfactants