scholarly journals Deletion of exon 4 from human surfactant protein C results in aggresome formation and generation of a dominant negative

2002 ◽  
Vol 116 (4) ◽  
pp. 683-692 ◽  
Author(s):  
W.-J. Wang
Keyword(s):  
Protein C ◽  
Surfactant Protein ◽  
Dominant Negative ◽  
Surfactant Protein C ◽  
Exon 4 ◽  
Aggresome Formation

Biosynthesis of surfactant protein C: characterization of aggresome formation by EGFP chimeras containing propeptide mutants lacking conserved cysteine residues

2001 ◽  
Vol 114 (2) ◽  
pp. 293-302
Author(s):  
A.F. Kabore ◽  
W.J. Wang ◽  
S.J. Russo ◽  
M.F. Beers
Keyword(s):  
Protein C ◽  
Transmembrane Protein ◽  
A549 Cells ◽  
Surfactant Protein ◽  
Mutant Protein ◽  
Cysteine Residues ◽  
Western Blots ◽  
Surfactant Protein C ◽  
C Terminus ◽  
Aggresome Formation

Surfactant protein C (SP-C) is a lung-specific secreted protein, which is synthesized as a 21-kDa propeptide (SP-C(21)) and then proteolytically processed as a bitopic transmembrane protein in subcellular compartments distal to the medial Golgi to produce a 3.7 kDa mature form. We have shown that initial processing of SP-C(21) involves two endoproteolytic cleavages of the C terminus and that truncation of nine amino acids from the C-flanking peptide resulted in retention of mutant protein in proximal compartments. Because these truncations involved removal of a conserved cysteine residue (Cys(186)), we hypothesized that intralumenal disulfide-mediated folding of the C terminus of SP-C(21) is required for intracellular trafficking. To test this, cDNA constructs encoding heterologous fusion proteins consisting of enhanced green fluorescent protein (EGFP) attached to the N terminus of wild-type rat proSP-C (EGFP/SP-C(1–194)), C-terminally deleted proSP-C (EGFP/SP-C(1–185); EGFP/SP-C(1–191)) or point mutations of conserved cysteine residues (EGFP/SP-C(C122G); EGFP/SP-C(C186G); or EGFP/SP-C(C122/186G)) were transfected into A549 cells. Fluorescence microscopy revealed that transfected EGFP/SP-C(1–194) and EGFP/SP-C(1–191)were expressed in a punctate pattern within CD-63 positive, EEA-1 negative cytoplasmic vesicles. In contrast, EGFP/SP-C(1–185), EGFP/SP-C(C122G), EGFP/SP-C(C186G) and EGFP/SP-C(C122/186G) were expressed but retained in a juxtanuclear compartment that stained for ubiquitin and that contained (γ)-tubulin and vimentin, consistent with expression in aggresomes. Treatment of cells transfected with mutant proSP-C with the proteasome inhibitor lactacysteine enhanced aggresome formation, which could be blocked by coincubation with nocodazole. Western blots using a GFP antibody detected a single form in lysates of cells transfected with EGFP/SP-C cysteine mutants, without evidence of smaller degradation fragments. We conclude that residues Cys(122) and Cys(186) of proSP-C are required for proper post-translational trafficking. Mutation or deletion of one or both of these residues results in misfolding with mistargeting of unprocessed mutant protein, leading to formation of stable aggregates within aggresomes.

Homozygous mutation in ABCA3 Lipid-Transporter defect (EXON 9) and low level of surfactant protein C

2010 ◽  
Vol 222 (S 01) ◽  
Author(s):  
J Pöschl ◽  
P Ruef ◽  
M Griese ◽  
P Lohse ◽  
C Aslanidis ◽  
...  
Keyword(s):  
Protein C ◽  
Surfactant Protein ◽  
Homozygous Mutation ◽  
Surfactant Protein C ◽  
Low Level ◽  
Exon 9 ◽  
Lipid Transporter

Influence of surfactant protein C on the interfacial behavior of phosphatidylethanolamine monolayers

2008 ◽  
Vol 38 (4) ◽  
pp. 369-379 ◽  
Author(s):  
Albena Jordanova ◽  
Georgi As. Georgiev ◽  
Svobodan Alexandrov ◽  
Roumen Todorov ◽  
Zdravko Lalchev
Keyword(s):  
Protein C ◽  
Surfactant Protein ◽  
Interfacial Behavior ◽  
Surfactant Protein C

scholarly journals TAZ Interacts with TTF-1 and Regulates Expression of Surfactant Protein-C

2004 ◽  
Vol 279 (17) ◽  
pp. 17384-17390 ◽  
Author(s):  
Kwon-Sik Park ◽  
Jeffrey A. Whitsett ◽  
Tina Di Palma ◽  
Jeong-Ho Hong ◽  
Michael B. Yaffe ◽  
...  
Keyword(s):  
Protein C ◽  
Surfactant Protein ◽  
Surfactant Protein C

scholarly journals Expression and Glucocorticoid Regulation of Surfactant Protein C in Human Fetal Lung

1997 ◽  
Vol 42 (3) ◽  
pp. 356-364 ◽  
Author(s):  
Kola O Solarin ◽  
Philip L Ballard ◽  
Susan H Guttentag ◽  
Catherine A Lomax ◽  
Michael F Beers
Keyword(s):  
Protein C ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Surfactant Protein C ◽  
Human Fetal Lung
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