ABSTRACT

The endoplasmic reticulum (ER) is a major site of protein folding. Perturbations in the folding capacity of the ER result in ER stress. ER stress triggers autophagic degradation of the ER (reticulophagy). Molecular mechanisms underlying ER stress-induced reticulophagy remain largely unknown. Our recent study identified a soluble protein, Epr1, as an autophagy receptor for ER stress-induced reticulophagy in the fission yeast Schizosaccharomyces pombe. Epr1 can interact simultaneously with Atg8 and a VAP family integral ER membrane protein, and thereby act as a bridging molecule between them. VAP family proteins contribute to reticulophagy by not only connecting Atg8 to the ER membrane through Epr1, but also by supporting the ER-plasma membrane contact. The expression of Epr1 is upregulated during ER stress in a manner dependent on the unfolded protein response (UPR) regulator Ire1. Ire1 promotes reticulophagy by upregulating Epr1.

摘要

内质网 (ER) 是蛋白质折叠的主要部位。ER 折叠能力的扰动导致 ER 应力。内质网应激触发内质网的自噬降解（网状自噬）。内质网应激诱导的网状吞噬的分子机制在很大程度上仍然未知。我们最近的研究确定了一种可溶性蛋白 Epr1，它是裂殖酵母粟酒裂殖酵母中内质网应激诱导的网状吞噬的自噬受体. Epr1 可以同时与 Atg8 和 VAP 家族内质网内质网膜蛋白相互作用，从而充当它们之间的桥接分子。VAP 家族蛋白不仅通过 Epr1 将 Atg8 连接到内质网膜，而且还通过支持内质网-质膜接触来促进网状吞噬。Epr1 的表达在内质网应激期间以依赖于未折叠蛋白反应 (UPR) 调节器 Ire1 的方式上调。Ire1 通过上调 Epr1 促进网状吞噬。