文章基本信息

标题：A virtuous cycle operated by ERp44 and ERGIC-53 guarantees proteostasis in the early secretory compartment
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作者：Tiziana Tempio ; Andrea Orsi ; Daria Sicari 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：3
页码：1-27
DOI：10.1016/j.isci.2021.102244
语种：English
出版社：Elsevier
摘要：SummaryThe composition of the secretome depends on the combined action of cargo receptors that facilitate protein transport and sequential checkpoints that restrict it to native conformers. Acting after endoplasmic reticulum (ER)-resident chaperones, ERp44 retrieves its clients from downstream compartments. To guarantee efficient quality control, ERp44 should exit the ER as rapidly as its clients, or more. Here, we show that appending ERp44 to different cargo proteins increases their secretion rates. ERp44 binds the cargo receptor ER-Golgi intermediate compartment (ERGIC)-53 in the ER to negotiate preferential loading into COPII vesicles. Silencing ERGIC-53, or competing for its COPII binding with 4-phenylbutyrate, causes secretion of Prdx4, an enzyme that relies on ERp44 for intracellular localization. In more acidic, zinc-rich downstream compartments, ERGIC-53 releases its clients and ERp44, which can bind and retrieve non-native conformers via KDEL receptors. By coupling the transport of cargoes and inspector proteins, cells ensure efficiency and fidelity of secretion.Graphical abstractDisplay OmittedHighlights•ERGIC-53 binds ERp44 and accelerates its exit from the ER•Genetic or pharmacological inhibition of ERGIC-53 impairs ERp44 retrieval function•ERp44 and ERGIC-53 form a functional couple needed for post-ER QCBiological Sciences; Biochemistry; Molecular Biology; Cell Biology