A yeast two-hybrid screening identifies novel Atg8a interactors in Drosophila.
A yeast two-hybrid screening identifies novel Atg8a interactors in Drosophila.
复制标题
酵母双杂交筛选鉴定了果蝇中新型 Atg8a 相互作用因子。
DOI：
10.1080/15548627.2022.2045535
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发表时间：
2022
期刊：
影响因子：
13.3
通讯作者：
Tsapras P
中科院分区：
文献类型：
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作者：
Tsapras P
自噬/自噬相关蛋白Atg8/Lc3在自噬小体的生物发生过程中起重要作用，是选择性降解各种底物所必需的。在我们最近的研究中，我们进行了酵母双杂交筛选，以确定与Atg8a相互作用的蛋白质，Atg8a是果蝇Atg8/LC3的同源物。筛选鉴定出几种与Atg8a相互作用的蛋白。这些蛋白质包括：i)已被实验证实与Atg8a结合的蛋白质，如Atg1、DOR、REF(2)P和Key(Kenny)；ii)其哺乳动物同源基因与Atg8家族成员相互作用的蛋白质，如Ank2、Atg4和Nedd4；以及iii)几个新的Atg8a相互作用蛋白，如TRC/STK38和Tak1。我们发现Tak1和它的共激活子Tab2都与Atg8a相互作用，是选择性自噬清除的底物。我们还确定SH3PX1与Tab2相互作用，是有效调节免疫缺陷(IMD)途径所必需的。我们的发现提示了Tak1-Tab2-SH3PX1和Atg8a之间的调节相互作用的机制，这有助于IMD途径的微调。
Macroautophagy/autophagy-related protein Atg8/LC3 is important for autophagosome biogenesis and required for selective degradation of various substrates. In our recent study, we performed a yeast two-hybrid screening to identify proteins that interact with Atg8a, theDrosophilahomolog of Atg8/LC3. The screening identified several Atg8a-interacting proteins. These proteins include: i) proteins which have already been experimentally verified to bind Atg8a, such as Atg1, DOR, ref(2)P and key (Kenny); ii) proteins for which their mammalian homologs interact with Atg8-family members, like Ank2, Atg4, and Nedd4; and iii) several novel Atg8a-interacting proteins, such as trc/STK38 and Tak1. We showed that Tak1, as well as its co-activator, Tab2, both interact with Atg8a and are substrates for selective autophagic clearance. We also determined that SH3PX1 interacts with Tab2 and is necessary for the effective regulation of the immune-deficiency (IMD) pathway. Our findings suggest a mechanism for the regulatory interactions between Tak1-Tab2-SH3PX1 and Atg8a, which contribute to the fine-tuning of the IMD pathway.