Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0668.
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0668
Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):E6237-E6244. doi: 10.1073/pnas.1805032115. Epub 2018 Jun 18.
The endoplasmic reticulum (ER) forms a contiguous network of tubules and sheets that is predominantly associated with the cell cortex in yeast. Upon treatment with rapamycin, the ER undergoes degradation by selective autophagy. This process, termed ER-phagy, requires Atg40, a selective autophagy receptor that localizes to the cortical ER. Here we report that ER-phagy also requires Lnp1, an ER membrane protein that normally resides at the three-way junctions of the ER network, where it serves to stabilize the network as it is continually remodeled. Rapamycin treatment increases the expression of Atg40, driving ER domains marked by Atg40 puncta to associate with Atg11, a scaffold protein needed to form autophagosomes. Although Atg40 largely localizes to the cortical ER, the autophagy machinery resides in the cell interior. The localization of Atg40 to sites of autophagosome formation is blocked in an Δ mutant or upon treatment of wild-type cells with the actin-depolymerizing drug Latrunculin A. This prevents the association of Atg40 with Atg11 and the packaging of the ER into autophagosomes. We propose that Lnp1 is needed to stabilize the actin-dependent remodeling of the ER that is essential for ER-phagy.
内质网（ER）形成一个连续的小管和薄片网络，主要与酵母的细胞皮层相关。在用雷帕霉素处理后，ER 通过选择性自噬进行降解。这个过程被称为 ER 自噬，需要 Atg40，一种选择性自噬受体，它定位于皮质 ER。在这里，我们报告 ER 自噬也需要 Lnp1，一种内质网膜蛋白，通常位于 ER 网络的三叉接头处，在那里它有助于稳定网络，因为它不断重塑。雷帕霉素处理增加了 Atg40 的表达，促使被 Atg40 斑点标记的 ER 域与 Atg11 结合，Atg11 是形成自噬体所必需的支架蛋白。尽管 Atg40 主要定位于皮质 ER，但自噬机制位于细胞内部。在Δ突变体或用肌动蛋白解聚药物 Latrunculin A 处理野生型细胞时，Atg40 向自噬体形成部位的定位被阻断。这阻止了 Atg40 与 Atg11 的结合和 ER 包装成自噬体。我们提出，Lnp1 对于稳定内质网的肌动蛋白依赖性重塑是必需的，这对于 ER 自噬至关重要。
