CHLOROQUINE DIVERTS ACTH FROM A REGULATED TO A CONSTITUTIVE SECRETORY PATHWAY IN ATT-20 CELLS
CHLOROQUINE DIVERTS ACTH FROM A REGULATED TO A CONSTITUTIVE SECRETORY PATHWAY IN ATT-20 CELLS
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DOI：
10.1038/302434a0
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发表时间：
1983-01-01
期刊：
影响因子：
64.8
通讯作者：
KELLY, RB
中科院分区：
文献类型：
--
作者：
MOORE, HP;GUMBINER, B;KELLY, RB
ATT-20细胞是一种小鼠垂体细胞系，它结构性地外化病毒膜糖蛋白和ACTH的前体，即不需要储存或调节就能迅速表达。它们也有一个受调控的途径，在这个途径中，它们将成熟激素ACTH和β-内啡肽2的前体裂解，将它们储存在分泌颗粒3中，只有在促分泌剂存在的情况下才能释放它们。类似于新合成的溶酶体酶，它们要么被输送到溶酶体，要么从细胞4，5分泌。靶向溶酶体可能需要一个低pH步骤，因为氯喹导致酶从细胞5，6分泌。在这里，我们发现氯喹(200微米)似乎也阻止了新合成的ACTH在分泌颗粒中的存储，而是通过结构性途径将其转移到细胞外。氯喹对ACTH的构成途径没有影响，也不阻断预包装的ACTH的胞吐作用。因此，就像溶酶体酶一样，在氯喹存在的情况下，肽激素不会被发送到正确的目的地，而是被转移到对氯喹不敏感的构成途径。
AtT-20 cells, a mouse pituitary line, externalize a viral membrane glycoprotein and the precursor of ACTH constitutively, that is, rapidly without storage or regulation1. They also have a regulated pathway in which they cleave the precursor to mature hormones, ACTH andβ-endorphin2, store them in secretory granules3and discharge them only in the presence of a secretagogue. An analogy exists for newly synthesized lysosomal enzymes which are either delivered to the lysosome or secreted from the cell4,5. Targeting to the lysosomes may require a lowpH step, since chloroquine causes the enzymes to be secreted from the cell5,6. Here we show that chloroquine (200 µM) also appears to block the storage of newly synthesized ACTH in secretory granules and instead diverts it to the outside of the cell via the constitutive pathway. Chloroquine has no effect on the constitutive pathway and does not block the exocytosis of pre-packaged ACTH. Thus like lysosomal enzymes, peptide hormones are not sent to their correct destinations in the presence of chloroquine, but are diverted instead to a constitutive pathway that is chloroquine-insensitive.