REQUIREMENT OF THE COLLAGENOUS DOMAIN FOR CARBOHYDRATE PROCESSING AND SECRETION OF A SURFACTANT PROTEIN, SP-A
REQUIREMENT OF THE COLLAGENOUS DOMAIN FOR CARBOHYDRATE PROCESSING AND SECRETION OF A SURFACTANT PROTEIN, SP-A
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DOI：
10.1016/0167-4889(88)90073-0
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发表时间：
1988-04-25
期刊：
影响因子：
--
通讯作者：
WHITSETT, JA
中科院分区：
文献类型：
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作者：
OREILLY, MA;NOGEE, L;WHITSETT, JA
在纯化的II型上皮细胞和大鼠肺中均发现两种不同的表面活性蛋白MR=35,000(SP-A)的胞内形式。在体内和体外，MR=30,000和34,000的高甘露糖前体构成了细胞内SP-A的重要部分。在含有内糖苷酶-H抗性唾液酸化形式的SP-A的板层体富集组分中发现了第二个胞内池。细胞内SP-A的转运和分泌不受糖加工抑制剂的影响。然而，与α，α‘’-联吡啶或顺-4-羟基-L-脯氨酸孵育的II型细胞，破坏胶原肽结构域内三螺旋的形成，抑制唾液酸化，细胞内转运到板层小体部分和分泌。在α、α‘-联吡啶或顺式-4-羟基-L-脯氨酸存在下，高甘露糖前体在细胞内积累，16-18h后不能分泌，因此，近端细胞内池中的高甘露糖前体(S)和板层体富集组分中的唾液酸化形式是SP-A在体外和体内的两种主要细胞内储存形式。SP-A通过依赖于多肽胶原区羟化的过程进行传递。SP-A的运输和分泌不依赖于天冬酰胺连接的碳水化合物的添加或加工。
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 .alpha.,.alpha.''-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 .alpha.,.alpha.''-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.