Moore H P
Ann N Y Acad Sci. 1987;493:50-61. doi: 10.1111/j.1749-6632.1987.tb27180.x.
Endocrine, exocrine, and neuronal cells package only a subset of their secretory products into the electron-dense secretory granules. To investigate the factors controlling selective packaging of proteins into these granules, we utilized the mouse pituitary tumor cell line, AtT-20, which retained the capability to sort adrenocorticotropic hormone (ACTH) into secretory granules in vitro. Packaging of ACTH was blocked by treatment with weak bases, but was unaffected when N-linked glycosylation or sulfation was inhibited. To test whether the targeting information is specified by sorting domains present on peptide hormone sequences, we determined if a protein could be diverted to the dense secretory granules by attachment to a peptide hormone sequence. A plasmid DNA was constructed that encoded a hybrid protein in which a fragment of a viral membrane protein was fused to the carboxy terminus of human growth hormone. AtT-20 cells transfected with the hybrid were found to target it to dense secretory vesicles efficiently. These results support the hypothesis that sorting domains on peptide hormones direct their packaging into dense secretory vesicles.
内分泌细胞、外分泌细胞和神经细胞仅将其分泌产物的一个子集包装到电子致密的分泌颗粒中。为了研究控制蛋白质选择性包装入这些颗粒的因素，我们利用了小鼠垂体肿瘤细胞系AtT-20，该细胞系在体外保留了将促肾上腺皮质激素（ACTH）分选到分泌颗粒中的能力。用弱碱处理可阻断ACTH的包装，但抑制N-连接糖基化或硫酸化时则不受影响。为了测试靶向信息是否由肽激素序列上存在的分选结构域指定，我们确定一种蛋白质是否可以通过与肽激素序列连接而被转移到致密分泌颗粒中。构建了一种质粒DNA，其编码一种杂合蛋白，其中病毒膜蛋白的一个片段与人生长激素的羧基末端融合。发现用该杂合蛋白转染的AtT-20细胞能有效地将其靶向致密分泌小泡。这些结果支持这样的假说，即肽激素上的分选结构域指导它们包装到致密分泌小泡中。
