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J. Biol. Chem., Vol. 276, Issue 18, 14658-14664, May 4, 2001
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From the 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 phopholipids 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 (
Secretion of Surfactant Protein C, an Integral Membrane
Protein, Requires the N-terminal Propeptide*
,,,,, and¶
Division of Pulmonary Biology, Children's
Hospital Medical Center, Cincinnati, Ohio 45229-3039 and the
§ Department of Functional Morphology, University of
Utrecht, 3508 TD Utrecht, The Netherlands
/) 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.
*
This work was supported by National Institutes of Health
Grants POI-HL6164 (to T. E. W.) and ROI-HL50046 (to S. W. G.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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