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Originally published In Press as doi:10.1074/jbc.M011770200 on January 30, 2001

J. Biol. Chem., Vol. 276, Issue 18, 14658-14664, May 4, 2001
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Secretion of Surfactant Protein C, an Integral Membrane Protein, Requires the N-terminal Propeptide*

Juliana Johnson ConkrightDagger , James P. BridgesDagger , Cheng-Lun NaDagger , Wim F. Voorhout§, Bruce TrapnellDagger , Stephan W. GlasserDagger , and Timothy E. WeaverDagger

From the Dagger  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

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 (-/-) 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.

To whom correspondence should be addressed: Children's Hospital Medical Center, Division of Pulmonary Biology, 3333 Burnet Ave., Cincinnati, OH 45229-3039. Tel.: 513-636-7223; Fax: 513-636-7868; E-mail: Tim.Weaver@chmcc.org.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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