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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Sterols block binding of COPII proteins to SCAP, thereby controlling SCAP sorting in ER
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Sterols block binding of COPII proteins to SCAP, thereby controlling SCAP sorting in ER

机译：甾醇阻止COPII蛋白与SCAP结合，从而控制ER中的SCAP分类

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摘要

Sterols inhibit their own synthesis in mammalian cells by blocking the vesicular endoplasmic reticulum-to-Golgi transport of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), a sterol-sensing protein that escorts SREBPs. Unable to reach the Golgi, SREBPs are not processed by Golgi-resident proteases, and they fail to activate genes required for cholesterol synthesis. The current studies were designed to reveal whether sterols block SCAP movement by inhibiting synthesis of special vesicles dedicated to SCAP, or whether sterols block SCAP incorporation into common coat protein (COP)ll-coated vesicles. Through immunoisolation, we show that SCAP-containing vesicles, formed in vitro, also contain vesicular stomatitis virus glycoprotein (VSVG) protein, a classic marker of COPII-coated vesicles. Sterols selectively block incorporation of SCAP into these vesicles without blocking incorporation of VSVG protein. We show that the mammalian vesicular budding reaction can be reconstituted by recom-binant yeast COPII proteins that support incorporation of SCAP as well as VSVG into vesicles. Sterols block SCAP incorporation into vesicles by blocking Sar1-dependent binding of the COPII proteins Sec 23/24 to SCAP. These studies demonstrate feedback control of a biosynthetic pathway by the regulated binding of COPII proteins to an endoplasmic reticulum-to-Golgi transport protein.
机译：甾醇通过阻断固醇调节元件结合蛋白（SREBP）裂解激活蛋白（SCAP）的囊泡内质网到高尔基体的运输来抑制哺乳动物细胞自身的合成，SCAP是一种伴有SREBPs的固醇感应蛋白。 SREBPs无法到达高尔基体，不会被高尔基体固定蛋白酶处理，它们无法激活胆固醇合成所需的基因。当前的研究旨在揭示固醇是否通过抑制专用于SCAP的特殊囊泡的合成来阻止SCAP的运动，或者固醇是否阻止SCAP掺入普通被膜蛋白（COP）11包裹的囊泡。通过免疫隔离，我们显示体外形成的含SCAP的囊泡还含有囊泡性口炎病毒糖蛋白（VSVG）蛋白，这是COPII包被囊泡的经典标记。甾醇选择性地阻止SCAP掺入这些囊泡中，而不会阻止VSVG蛋白的掺入。我们表明，哺乳动物的水泡出芽反应可以通过重组酵母COPII蛋白来重建，该蛋白支持SCAP和VSVG并入囊泡中。甾醇通过阻止COPII蛋白Sec 23/24与SCAP的Sar1依赖性结合来阻止SCAP结合到囊泡中。这些研究表明，通过COPII蛋白与内质网到高尔基体转运蛋白的调节结合，可以控制生物合成途径。

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