D'Arcangelo Jennifer G, Crissman Jonathan, Pagant Silvere, Čopič Alenka, Latham Catherine F, Snapp Erik L, Miller Elizabeth A
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Curr Biol. 2015 May 18;25(10):1296-305. doi: 10.1016/j.cub.2015.03.029. Epub 2015 Apr 30.
Eukaryotic protein secretion requires efficient and accurate delivery of diverse secretory and membrane proteins. This process initiates in the ER, where vesicles are sculpted by the essential COPII coat. The Sec13p subunit of the COPII coat contributes to membrane scaffolding, which enforces curvature on the nascent vesicle. A requirement for Sec13p can be bypassed when traffic of lumenally oriented membrane proteins is abrogated. Here we sought to further explore the impact of cargo proteins on vesicle formation. We show that efficient ER export of the p24 family of proteins is a major driver of the requirement for Sec13p. The scaffolding burden presented by the p24 complex is met in part by the cargo adaptor Lst1p, which binds to a subset of cargo, including the p24 proteins. We propose that the scaffolding function of Lst1p is required to generate vesicles that can accommodate difficult cargo proteins that include large oligomeric assemblies and asymmetrically distributed membrane proteins. Vesicles that contain such cargoes are also more dependent on scaffolding by Sec13p, and may serve as a model for large carrier formation in other systems.
真核生物的蛋白质分泌需要高效且准确地运输多种分泌蛋白和膜蛋白。这个过程始于内质网，在那里囊泡由必需的COPII衣被塑造。COPII衣被的Sec13p亚基有助于膜支架的形成，从而使新生囊泡产生曲率。当腔内定向膜蛋白的运输被消除时，对Sec13p的需求可以被绕过。在这里，我们试图进一步探索货物蛋白对囊泡形成的影响。我们表明，p24蛋白家族的高效内质网输出是对Sec13p需求的主要驱动因素。p24复合体呈现的支架负担部分由货物衔接蛋白Lst1p承担，Lst1p与包括p24蛋白在内的一部分货物结合。我们提出，Lst1p的支架功能是生成能够容纳困难货物蛋白（包括大型寡聚体组装体和不对称分布的膜蛋白）的囊泡所必需的。含有此类货物的囊泡也更依赖于Sec13p的支架作用，并且可能作为其他系统中大型载体形成的模型。
