Atlastins remodel the endoplasmic reticulum for selective autophagy.
Atlastins remodel the endoplasmic reticulum for selective autophagy.
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DOI：
10.1083/jcb.201804185
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发表时间：
2018-10-01
期刊：
影响因子：
--
通讯作者：
Corn JE
中科院分区：
文献类型：
--
作者：
Liang JR;Lingeman E;Ahmed S;Corn JE
最近报道了多种ER-吞噬受体，但其他介质或调节剂仍然难以捉摸。Liang等人开发了两种ER-吞噬特异性报告基因测定，并表明Atlastins（ER表面GTP酶家族）是ER-吞噬的正调节因子，作用于ER-吞噬受体FAM 134 B的下游。内质网（ER）的自噬降解需要特异性受体，称为ER-吞噬。然而，很少有人知道ER是如何重塑和分离包装成自噬体。我们开发了两个ER-吞噬特异性报告系统，发现Atlastins是关键的正效应子，也是ER-吞噬的靶点。Atlastins是参与ER膜形态的ER驻留GTP酶，并且Atlastin耗尽的细胞在饥饿条件下具有降低的ER吞噬。在ER-吞噬中，Ekastin的作用需要一个功能性的GT3结构域和适当的ER定位，这两者也参与ER结构。这三个Escherastin家族成员在ER-吞噬过程中功能性地相互补偿，并且可以相互形成异聚复合物。我们进一步发现，Atlastins作用于FAM 134 B ER-吞噬受体的下游，使得Atlastins的消耗抑制由FAM 134 B的过表达诱导的ER-自噬。我们认为在ER-吞噬过程中，Atlastins重塑ER膜以分离FAM 134 B标记的ER片段，以实现有效的自噬体吞噬。
Multiple ER-phagy receptors have been reported recently, but other mediators or regulators have remained elusive. Liang et al. developed two ER-phagy–specific reporter assays and showed that Atlastins, a family of ER surface GTPases, are positive regulators of ER-phagy that act downstream of an ER-phagy receptor, FAM134B. Specific receptors are required for the autophagic degradation of endoplasmic reticulum (ER), known as ER-phagy. However, little is known about how the ER is remodeled and separated for packaging into autophagosomes. We developed two ER-phagy–specific reporter systems and found that Atlastins are key positive effectors and also targets of ER-phagy. Atlastins are ER-resident GTPases involved in ER membrane morphology, and Atlastin-depleted cells have decreased ER-phagy under starvation conditions. Atlastin’s role in ER-phagy requires a functional GTPase domain and proper ER localization, both of which are also involved in ER architecture. The three Atlastin family members functionally compensate for one another during ER-phagy and may form heteromeric complexes with one another. We further find that Atlastins act downstream of the FAM134B ER-phagy receptor, such that depletion of Atlastins represses ER-autophagy induced by the overexpression of FAM134B. We propose that during ER-phagy, Atlastins remodel ER membrane to separate pieces of FAM134B-marked ER for efficient autophagosomal engulfment.
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DOI：
10.1016/j.cub.2017.01.047
发表时间：
2017-03-06
期刊：
Current biology : CB
影响因子：
--
作者：
Bastide A;Peretti D;Knight JR;Grosso S;Spriggs RV;Pichon X;Sbarrato T;Roobol A;Roobol J;Vito D;Bushell M;von der Haar T;Smales CM;Mallucci GR;Willis AE
通讯作者：
Willis AE
影响因子：
64.5
作者：
Brodsky JL
通讯作者：
Brodsky JL
影响因子：
16.2
作者：
Pickrell AM;Youle RJ
通讯作者：
Youle RJ
影响因子：
13.3
作者：
Gegg ME;Schapira AH
通讯作者：
Schapira AH
影响因子：
11.4
作者：
Klopfenstein, DRC;Kappeler, F;Hauri, HP
通讯作者：
Hauri, HP