A COPII subunit acts with an autophagy receptor to target endoplasmic reticulum for degradation
A COPII subunit acts with an autophagy receptor to target endoplasmic reticulum for degradation
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DOI：
10.1126/science.aau9263
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发表时间：
2019-07-05
期刊：
影响因子：
56.9
通讯作者：
Ferro-Novick, Susan
中科院分区：
文献类型：
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作者：
Cui, Yixian;Parashar, Smriti;Ferro-Novick, Susan
COPII-Cargo适配器复合体Lst1-Sec23选择性地将蛋白质分类成小泡，这些小泡从内质网(ER)萌芽并运输到高尔基体。折叠不当的蛋白质会被阻止离开内质网，并被降解。内质网吞噬是一种利用内质网驻留受体的自噬降解途径。在酵母中，我们发现了Lst1-Sec23在ER吞噬中的一个意想不到的作用，这种作用独立于它在分泌中的功能。应激诱导的ER吞噬受体Atg40的上调诱导Lst1-Sec23与不同ER结构域的Atg40结合，将ER包装成自噬小体。Lst1介导的内质网吞噬作用通过阻止内质网中易于聚集的蛋白质的积累，在维持细胞内稳态方面发挥了至关重要的作用。Lst1的功能似乎是保守的，因为它的哺乳动物同源基因SEC24C也是ER吞噬所必需的。
The COPII-cargo adaptor complex Lst1-Sec23 selectively sorts proteins into vesicles that bud from the endoplasmic reticulum (ER) and traffic to the Golgi. Improperly folded proteins are prevented from exiting the ER and are degraded. ER-phagy is an autophagic degradation pathway that uses ER-resident receptors. Working in yeast, we found an unexpected role for Lst1-Sec23 in ER-phagy that was independent from its function in secretion. Up-regulation of the stress-inducible ER-phagy receptor Atg40 induced the association of Lst1-Sec23 with Atg40 at distinct ER domains to package ER into autophagosomes. Lst1-mediated ER-phagy played a vital role in maintaining cellular homeostasis by preventing the accumulation of an aggregationprone protein in the ER. Lst1 function appears to be conserved because its mammalian homolog, SEC24C, was also required for ER-phagy.