Secretion of surfactant protein C, an integral membrane protein, requires the N-terminal propeptide
Secretion of surfactant protein C, an integral membrane protein, requires the N-terminal propeptide
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DOI：
10.1074/jbc.m011770200
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发表时间：
2001-05-04
影响因子：
4.8
通讯作者：
Weaver, TE
中科院分区：
文献类型：
--
作者：
Conkright, JJ;Bridges, JP;Weaver, TE
肺泡II型细胞的多泡体中的表面活性蛋白C（SP-C）前蛋白的蛋白水解加工导致35个残基的成熟肽，由跨膜结构域和10个残基的膜外结构域组成。SP-C成熟肽储存在板层体（溶酶体样细胞器）中，并与表面活性剂磷脂一起分泌到肺泡腔中。本研究旨在确定SP-C的肽结构域所需的分选和分泌的这种完整的膜肽。瞬时转染的PC 12细胞和分离的小鼠II型细胞的缺失分析表明，成熟SP-C的膜外结构域是胞质的，足以分选到受调节的分泌途径。经气管内注射编码SP-C成熟肽的腺病毒，可使SP-C分泌进入野生型小鼠的肺泡腔，但不能进入SP-C（-/-）小鼠的肺泡腔，而加入N端前肽可使缺失小鼠的SP-C分泌恢复。支持血小板衍生生长因子受体的跨膜结构域的分泌。总的来说，这些研究表明SP-C的N-末端前肽对于SP-C的细胞内分选和分泌是必需的。
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.