Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation.
Efficient secretion of small proteins in mammalian cells relies on Sec62-dependent posttranslational translocation.
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DOI：
10.1091/mbc.e12-03-0228
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发表时间：
2012-07
影响因子：
3.3
通讯作者：
Strub K
中科院分区：
文献类型：
--
作者：
Lakkaraju AK;Thankappan R;Mary C;Garrison JL;Taunton J;Strub K
该研究揭示了哺乳动物Sec 62在ER易位中的作用。它阐明了SRP和Sec 62依赖性易位途径之间的选择，表明短蛋白依赖于Sec 62，而长于160个氨基酸的蛋白依赖于SRP以获得最大易位效率，这意味着Sec 62途径是小前蛋白的故障安全途径。哺乳动物细胞分泌大量的小分子蛋白质，但它们转运到内质网的方式还不完全清楚。由于信号识别颗粒（SRP）识别信号序列的时间窗口很小，预期共翻译易位是低效的。通过RNA干扰损害SRP途径并降低易位子组分Sec 62的细胞水平，我们在哺乳动物细胞中发现了一种替代的Sec 62依赖性易位途径，该途径是具有N-末端信号序列的小蛋白质有效易位所需的。Sec 62依赖性易位通过Sec 61易位子在产后发生，并需要ATP。我们将前蛋白分为三组：1）包含≤100个氨基酸的前蛋白强烈依赖于Sec 62进行有效易位; 2）大小在120-160个氨基酸范围内的前蛋白使用SRP途径，尽管效率低下，因此依赖于Sec 62进行有效易位;和3）大于160个氨基酸的那些依赖于SRP途径以保持不依赖于Sec 62的瞬时易位能力。因此，与酵母不同，哺乳动物细胞中的Sec 62依赖性易位途径主要用作确保小蛋白质的有效分泌的故障安全机制，并为细胞提供了独立于SRP途径调节小蛋白质分泌的机会。
The study reveals a role of mammalian Sec62 in ER translocation. It elucidates the choice between SRP- and Sec62-dependent translocation routes, showing that short proteins rely on Sec62 and proteins longer than 160 amino acids rely on SRP for maximal translocation efficiency, implying that the Sec62 path is a fail-safe route for small preproteins. Mammalian cells secrete a large number of small proteins, but their mode of translocation into the endoplasmic reticulum is not fully understood. Cotranslational translocation was expected to be inefficient due to the small time window for signal sequence recognition by the signal recognition particle (SRP). Impairing the SRP pathway and reducing cellular levels of the translocon component Sec62 by RNA interference, we found an alternate, Sec62-dependent translocation path in mammalian cells required for the efficient translocation of small proteins with N-terminal signal sequences. The Sec62-dependent translocation occurs posttranslationally via the Sec61 translocon and requires ATP. We classified preproteins into three groups: 1) those that comprise ≤100 amino acids are strongly dependent on Sec62 for efficient translocation; 2) those in the size range of 120–160 amino acids use the SRP pathway, albeit inefficiently, and therefore rely on Sec62 for efficient translocation; and 3) those larger than 160 amino acids depend on the SRP pathway to preserve a transient translocation competence independent of Sec62. Thus, unlike in yeast, the Sec62-dependent translocation pathway in mammalian cells serves mainly as a fail-safe mechanism to ensure efficient secretion of small proteins and provides cells with an opportunity to regulate secretion of small proteins independent of the SRP pathway.
酵母微粒体膜上的蛋白质易位受到可溶性因子的刺激。
影响因子：
7.8
作者：
WATERS, MG;CHIRICO, WJ;BLOBEL, G
通讯作者：
BLOBEL, G