TRC40 can deliver short secretory proteins to the Sec61 translocon.

TRC40 can deliver short secretory proteins to the Sec61 translocon.
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DOI:
10.1242/jcs.102608
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发表时间:
2012-08-01
影响因子:
4
通讯作者:
High S
High S
中科院分区:
生物学2区
文献类型:
--
作者:
Johnson N;Vilardi F;Lang S;Leznicki P;Zimmermann R;High S

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虽然新生蛋白质在哺乳动物内质网(ER)之间的共翻译易位已经被很好地定义,但这个细胞器对翻译后易位的能力却没有被很好地描述。在这里,我们确定了两种人类分泌蛋白前体,apelin和statherin,作为翻译后跨ER膜转位的真正底物。进一步的研究,结合透明藻前原蛋白A(PpcecA),表明所有三种蛋白质都与TRC40结合,并可以利用这一成分在良好的体外系统中将其输送到内质网膜上。然而,ppcecA不是专有的TRC40底物,它也可以通过另一条不依赖TRC40的途径输送到内质网。当这些短的分泌蛋白到达内质网膜时,似乎无处不在地通过Sec61转运子跨越内质网膜运输,显然与它们的传递途径无关。我们推测,在高等真核生物中,分泌蛋白的翻译后易位比以前所承认的更普遍。
Whilst the co-translational translocation of nascent proteins across the mammalian endoplasmic reticulum (ER) is well defined, the capacity of this organelle for post-translational translocation is poorly delineated. Here we identify two human secretory protein precursors, apelin and statherin, as bona fide substrates for post-translational translocation across the ER membrane. Further studies, in combination with Hyalophora cecropia preprocecropin A (ppcecA), show that all three proteins bind to TRC40 and can utilise this component for their delivery to the ER membrane in a well-established in vitro system. However, ppcecA is not an obligate TRC40 substrate, and it can also be delivered to the ER by an alternative TRC40-independent pathway. Upon arrival at the ER membrane, these short secretory proteins appear to be ubiquitously transported across the ER membrane through the Sec61 translocon, apparently irrespective of their delivery route. We speculate that the post-translational translocation of secretory proteins in higher eukaryotes is more prevalent than previously acknowledged.
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