TY - JOUR
T1 - Requirement of the collagenous domain for carbohydrate processing and secretion of a surfactant protein, SP-A
AU - O'Reilly, Michael A.
AU - Nogee, Lawrence
AU - Whitsett, Jeffrey A.
N1 - Funding Information:
This work was supported in part by Research Career Development Award HL-10124 (J.A.W.) from the National Institutes of Health, by HL-28623, HD-11725. M.O.R. was funded in part by a Molecular and Cellular Biology Training Grant, HL-07527. The authors would like to acknowledge Winston Kao, Ph.D. for his helpful suggestions.
PY - 1988/4/25
Y1 - 1988/4/25
N2 - Two distinct intracellular forms of surfactant protein Mr = 35 000 (SP-A) were demonstrated in both purified type II epithelial cells and rat lung in vivo. High-mannose precursors of Mr = 30 000 and 34 000 comprised a significant fraction of intracellular SP-A in vivo and in vitro. A second intracellular pool was demonstrated in lamellar body enriched fractions which contained endoglycosidase-H resistant, sialylated forms of SP-A. Intracellular transport and secretion of SP-A was not altered by inhibitors of carbohydrate processing. However, incubation of type II cells with α,α′-dipyridyl or cis-4-hydroxy-l-proline, agents which disrupt triple-helix formation within collagenous peptide domains, inhibited sialylation, intracellular transport to the lamellar body fraction and secretion. In the presence of either α,α′-dipyridyl or cis-4-hydroxy-l-proline, high mannose precursors accumulated intracellularly and were not secreted after 16-18 h. Thus, high-mannose precursors in proximal intracellular pool(s) and sialylated forms in lamellar body-enriched fractions represent two major intracellular storage forms of SP-A in vitro and in vivo. SP-A is routed by processes dependent upon the hydroxylation of the collagenous domain of the polypeptide. Transport and secretion of SP-A are not dependent upon the addition or processing of asparagine-linked carbohydrate.
AB - Two distinct intracellular forms of surfactant protein Mr = 35 000 (SP-A) were demonstrated in both purified type II epithelial cells and rat lung in vivo. High-mannose precursors of Mr = 30 000 and 34 000 comprised a significant fraction of intracellular SP-A in vivo and in vitro. A second intracellular pool was demonstrated in lamellar body enriched fractions which contained endoglycosidase-H resistant, sialylated forms of SP-A. Intracellular transport and secretion of SP-A was not altered by inhibitors of carbohydrate processing. However, incubation of type II cells with α,α′-dipyridyl or cis-4-hydroxy-l-proline, agents which disrupt triple-helix formation within collagenous peptide domains, inhibited sialylation, intracellular transport to the lamellar body fraction and secretion. In the presence of either α,α′-dipyridyl or cis-4-hydroxy-l-proline, high mannose precursors accumulated intracellularly and were not secreted after 16-18 h. Thus, high-mannose precursors in proximal intracellular pool(s) and sialylated forms in lamellar body-enriched fractions represent two major intracellular storage forms of SP-A in vitro and in vivo. SP-A is routed by processes dependent upon the hydroxylation of the collagenous domain of the polypeptide. Transport and secretion of SP-A are not dependent upon the addition or processing of asparagine-linked carbohydrate.
KW - (Lamellar body)
KW - Collagenous domain
KW - Glycosylation
KW - Surfactant protein
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U2 - 10.1016/0167-4889(88)90073-0
DO - 10.1016/0167-4889(88)90073-0
M3 - Article
C2 - 3355864
AN - SCOPUS:0023921010
SN - 0167-4889
VL - 969
SP - 176
EP - 184
JO - BBA - Molecular Cell Research
JF - BBA - Molecular Cell Research
IS - 2
ER -