Ubiquitin-specific protease 8 deubiquitinates Sec31A and decreases large COPII carriers and collagen IV secretion
Ubiquitin-specific protease 8 deubiquitinates Sec31A and decreases large COPII carriers and collagen IV secretion
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DOI：
10.1016/j.bbrc.2018.03.202
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发表时间：
2018-05-15
影响因子：
3.1
通讯作者：
Komada, Masayuki
中科院分区：
文献类型：
--
作者：
Kawaguchi, Kohei;Endo, Akinori;Komada, Masayuki
内质网中的新生货物蛋白由 COPII 载体转运至高尔基体。典型的 COPII 囊泡直径为 60-70 nm，更大的大分子（例如前胶原）由哺乳动物细胞中的非典型大 COPII 载体运输。 Cu13 泛素连接酶可单泛素化 COPII 外壳蛋白 Sec31A，从而增强大型 COPII 载体的形成。然而，Sec31A 的去泛素化酶尚不清楚。在这里，我们证明去泛素化酶 USP8 与 Sec31A 相互作用并使 Sec31A 去泛素化。这种相互作用是由接头蛋白 STAM1 介导的。 USP8 过表达抑制大 COPII 载体的形成。相比之下，USP8敲低导致COPII外壳蛋白在顺式高尔基体周围积累，促进IV原胶原从内质网到高尔基体的细胞内运输，并增加IV胶原的分泌。我们得出结论，USP8 使 Sec31A 去泛素化并抑制大 COPII 载体的形成，从而抑制 IV 型胶原蛋白的分泌。 (C) 2018 Elsevier Inc. 保留所有权利。
Nascent cargo proteins in the endoplasmic reticulum are transported to the Golgi by COPII carriers. Typical COPII vesicles are 60-70 nm in diameter, and much larger macromolecules, such as procollagen, are transported by atypical large COPII carriers in mammalian cells. The formation of large COPII carriers is enhanced by Cu13 ubiquitin ligase, which mono-ubiquitinates Sec31A, a COPII coat protein. However, the deubiquitinating enzyme for Sec31A was unclear. Here, we show that the deubiquitinating enzyme USP8 interacts with and deubiquitinates Sec31A. The interaction was mediated by the adaptor protein STAM1. USP8 overexpression inhibited the formation of large COPII carriers. By contrast, USP8 knockdown caused the accumulation of COPII coat proteins around the cis-Golgi, promoted the intracellular trafficking of procollagen IV from the endoplasmic reticulum to the Golgi, and increased collagen IV secretion. We concluded that USP8 deubiquitinates Sec31A and inhibits the formation of large COPII carriers, thereby suppressing collagen IV secretion. (C) 2018 Elsevier Inc. All rights reserved.