Atg9 establishes Atg2-dependent contact sites between the endoplasmic reticulum and phagophores.
Atg9 establishes Atg2-dependent contact sites between the endoplasmic reticulum and phagophores.
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DOI：
10.1083/jcb.201710116
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发表时间：
2018-08-06
期刊：
影响因子：
--
通讯作者：
Reggiori F
中科院分区：
文献类型：
--
作者：
Gómez-Sánchez R;Rose J;Guimarães R;Mari M;Papinski D;Rieter E;Geerts WJ;Hardenberg R;Kraft C;Ungermann C;Reggiori F
Atg2， Atg18和Atg9对自噬很重要，但它们的确切功能尚不清楚。Gómez-Sánchez等人研究了不能与Atg9结合的Atg2突变体，并表明与Atg9的相互作用将Atg2限制在扩张的吞噬体的末端，Atg9 - Atg2 - atg18复合物的组装在建立吞噬体-内质网接触位点中起作用。自噬相关蛋白（Atg）在自噬体的形成中起关键作用，自噬体是自噬的标志。尽管Atg2、Atg18和跨膜Atg9在自噬中起重要作用，但它们的功能完全未知。在这项研究中，我们通过鉴定和表征Atg2点突变体在Atg9结合中受损，从而深入了解了这些蛋白质的分子作用。我们发现Atg2通过脂质结合与自噬体膜结合，独立于Atg9。然而，它与Atg9的相互作用是Atg2限制生长的吞噬体末端和随后与Atg18结合的关键。Atg9-Atg2-Atg18复合物的组装对于建立吞噬体-内质网（ER）接触位点非常重要。反过来，Atg2 - atg9相互作用的破坏导致Atg2和ER在形成吞噬团时接触位点的拓扑分布异常，这严重损害了自噬。总之，我们的数据揭示了Atg9， Atg2和Atg18之间的相互关系，并强调了吞噬体- er接触位点在吞噬体扩展中的可能功能相关性。
Atg2, Atg18, and Atg9 are important for autophagy, but their precise functions are unclear. Gómez-Sánchez et al. study Atg2 mutants unable to bind to Atg9 and show that the interaction with Atg9 confines Atg2 to the extremities of the expanding phagophore and that the assembly of the Atg9–Atg2–Atg18 complex plays a role in establishing phagophore–endoplasmic reticulum contact sites. The autophagy-related (Atg) proteins play a key role in the formation of autophagosomes, the hallmark of autophagy. The function of the cluster composed by Atg2, Atg18, and transmembrane Atg9 is completely unknown despite their importance in autophagy. In this study, we provide insights into the molecular role of these proteins by identifying and characterizing Atg2 point mutants impaired in Atg9 binding. We show that Atg2 associates to autophagosomal membranes through lipid binding and independently from Atg9. Its interaction with Atg9, however, is key for Atg2 confinement to the growing phagophore extremities and subsequent association of Atg18. Assembly of the Atg9–Atg2–Atg18 complex is important to establish phagophore–endoplasmic reticulum (ER) contact sites. In turn, disruption of the Atg2–Atg9 interaction leads to an aberrant topological distribution of both Atg2 and ER contact sites on forming phagophores, which severely impairs autophagy. Altogether, our data shed light in the interrelationship between Atg9, Atg2, and Atg18 and highlight the possible functional relevance of the phagophore–ER contact sites in phagophore expansion.
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