ESCRT-III drives the final stages of CUPS maturation for unconventional protein secretion
ESCRT-III drives the final stages of CUPS maturation for unconventional protein secretion
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DOI：
10.7554/elife.16299
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发表时间：
2016-04-26
期刊：
影响因子：
7.7
通讯作者：
Malhotra, Vivek
中科院分区：
文献类型：
--
作者：
Curwin, Amy J.;Brouwers, Nathalie;Malhotra, Vivek
非常规的分泌途径输出绕过内质网的蛋白质。在酿酒酵母中，通过该途径触发Acb 1分泌的条件产生包含Grh 1的隔室，该隔室由被杯状膜包围的囊泡和小管组成，统称为CUPS。在这里，我们报告的Acb 1分泌的定量测定，揭示了ESCRT-I，-II和-III的要求，但令人惊讶的是，没有参与的Vps 4 AAA-ATPase。主要的ESCRT-II I亚基Snf 7瞬时定位于CUPS，这在vps 4A细胞中加速，与Acbl分泌增加相关。显微镜分析表明，ESCRT-III/Snf 7不是在Vps 4的帮助下形成管腔内囊泡，而是促进预先存在的含有囊泡和小管的Grh 1直接吞噬到球囊中，以产生成熟的含有Acb 1的隔室。这种新的多泡/多层室，我们建议代表CUPS的稳定分泌形式，是主管释放Acb 1到细胞外部。
The unconventional secretory pathway exports proteins that bypass the endoplasmic reticulum. In Saccharomyces cerevisiae, conditions that trigger Acb1 secretion via this pathway generate a Grh1 containing compartment composed of vesicles and tubules surrounded by a cup shaped membrane and collectively called CUPS. Here we report a quantitative assay for Acb1 secretion that reveals requirements for ESCRT-I, -II, and -III but, surprisingly, without the involvement of the Vps4 AAA-ATPase. The major ESCRT-II I subunit Snf7 localizes transiently to CUPS and this was accelerated in vps4A cells, correlating with increased Acbl secretion. Microscopic analysis suggests that, instead of forming intraluminal vesicles with the help of Vps4, ESCRT-III/Snf7 promotes direct engulfment of preexisting Grh1 containing vesicles and tubules into a saccule to generate a mature Acb1 containing compartment. This novel multivesicular / multilamellar compartment, we suggest represents the stable secretory form of CUPS that is competent for the release of Acb1 to cells exterior.