The prodomain of a secreted hydrophobic mini-protein facilitates its export from the endoplasmic reticulum by hitchhiking on sorting receptors
The prodomain of a secreted hydrophobic mini-protein facilitates its export from the endoplasmic reticulum by hitchhiking on sorting receptors
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DOI：
10.1074/jbc.c300141200
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发表时间：
2003-07-18
影响因子：
4.8
通讯作者：
Fainzilber, M
中科院分区：
文献类型：
--
作者：
Conticello, SG;Kowalsman, ND;Fainzilber, M
错误折叠的分泌蛋白通过针对暴露的疏水表面的质量控制机制保留在内质网(ER)中。矛盾的是，某些芋螺毒素在折叠到其生物活性结构时暴露出广泛的疏水表面。那么，这种分泌的微型蛋白质是如何通过分泌途径的呢？在这里，我们证明了疏水性芋螺毒素-TxVI的分泌强烈依赖于它的前肽结构域，这促进了TxVI从内质网的输出。前肽结构域与山梨素Vps10p结构域家族的分选受体相互作用。山梨素-TxVI相互作用发生在内质网中，山梨素促进了TxVI从内质网向高尔基体的输出。因此，分泌的疏水蛋白中的原结构域可以作为一个标签，通过搭便车机制促进其内质网的输出。
Misfolded secretory proteins are retained in the endoplasmic reticulum ( ER) by quality control mechanisms targeted to exposed hydrophobic surfaces. Paradoxically, certain conotoxins expose extensive hydrophobic surfaces upon folding to their bioactive structures. How then can such secreted mini-proteins traverse the secretory pathway? Here we show that secretion of the hydrophobic conotoxin-TxVI is strongly dependent on its propeptide domain, which enhances TxVI export from the ER. The propeptide domain interacts with sorting receptors from the sortilin Vps10p domain family. The sortilin-TxVI interaction occurs in the ER, and sortilin facilitates export of TxVI from the ER to the Golgi. Thus, the prodomain in a secreted hydrophobic protein acts as a tag that can facilitate its ER export by a hitchhiking mechanism.