Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Mol Biol Cell. 2010 May 1;21(9):1556-68. doi: 10.1091/mbc.e09-12-1002. Epub 2010 Mar 17.
The structure of the endoplasmic reticulum (ER) undergoes highly regulated changes in specialized cell types. One frequently observed type of change is its reorganization into stacked and concentrically whorled membranes, but the underlying mechanisms and functional relevance for cargo export are unknown. Here, we identify Yip1A, a conserved membrane protein that cycles between the ER and early Golgi, as a key mediator of ER organization. Yip1A depletion led to restructuring of the network into multiple, micrometer-sized concentric whorls. Membrane stacking and whorl formation coincided with a marked slowing of coat protein (COP)II-mediated protein export. Furthermore, whorl formation driven by exogenous expression of an ER protein with no role in COPII function also delayed cargo export. Thus, the slowing of protein export induced by Yip1A depletion may be attributed to a proximal role for Yip1A in regulating ER network dispersal. The ER network dispersal function of Yip1A was blocked by alteration of a single conserved amino acid (E95K) in its N-terminal cytoplasmic domain. These results reveal a conserved Yip1A-mediated mechanism for ER membrane organization that may serve to regulate cargo exit from the organelle.
内质网（ER）的结构在特化细胞类型中经历高度调控的变化。一种常见的变化类型是其重组为堆叠的同心轮状膜，但对于货物出口的潜在机制和功能相关性尚不清楚。在这里，我们确定了 Yip1A，一种在 ER 和早期高尔基体之间循环的保守膜蛋白，是 ER 组织的关键介质。Yip1A 的耗竭导致网络重组为多个微米大小的同心轮。膜堆叠和轮形成与包裹蛋白 (COP)II 介导的蛋白质出口明显减慢同时发生。此外，由没有 COPII 功能的 ER 蛋白的外源表达驱动的轮形成也延迟了货物出口。因此，Yip1A 耗竭诱导的蛋白质出口减缓可能归因于 Yip1A 在调节 ER 网络分散中的近端作用。通过改变其 N 端细胞质结构域中的单个保守氨基酸（E95K），Yip1A 的 ER 网络分散功能被阻断。这些结果揭示了一种保守的 Yip1A 介导的 ER 膜组织机制，可能有助于调节货物从细胞器中排出。
