PDZD8 interacts with Protrudin and Rab7 at ER-late endosome membrane contact sites associated with mitochondria
PDZD8 interacts with Protrudin and Rab7 at ER-late endosome membrane contact sites associated with mitochondria
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DOI：
10.1038/s41467-020-17451-7
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发表时间：
2020-07-20
影响因子：
16.6
通讯作者：
Nunnari, Jodi
中科院分区：
文献类型：
--
作者：
Elbaz-Alon, Yael;Guo, Yuting;Nunnari, Jodi
内体是组成动态的细胞器，通过指定进入细胞的物质是否会被穿梭回细胞表面或被溶酶体降解来调节信号、营养状态和细胞器质量。近年来，内质网(ER)和内体之间的膜接触部位(MCSs)在内体蛋白的分选、动力学和运动中起着重要的作用。在这里，我们证明了PDZD8，一个含有突触素样线粒体脂结合蛋白(SMP)结构域的ER跨膜蛋白，利用不同的结构域与Rab7-GTP和ER跨膜蛋白Protrudin相互作用，这些成分一起定位于ER晚期的内体MCS。在这些内质网晚期的内体MCS上，线粒体也被招募以形成三向接触。因此，我们的数据表明，PDZD8是两个不同的MCSs的共同成分，并表明SMP介导的脂质运输在调节内体功能中发挥了作用。细胞器之间的膜接触部位已被证明发挥着重要的生物学作用。在这里，作者发现在内质网，PDZD8与Protrudin结合，也与Rab7内体结合，并招募线粒体形成三向接触。
Endosomes are compositionally dynamic organelles that regulate signaling, nutrient status and organelle quality by specifying whether material entering the cells will be shuttled back to the cell surface or degraded by the lysosome. Recently, membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and endosomes have emerged as important players in endosomal protein sorting, dynamics and motility. Here, we show that PDZD8, a Synaptotagmin-like Mitochondrial lipid-binding Proteins (SMP) domain-containing ER transmembrane protein, utilizes distinct domains to interact with Rab7-GTP and the ER transmembrane protein Protrudin and together these components localize to an ER-late endosome MCS. At these ER-late endosome MCSs, mitochondria are also recruited to form a three-way contact. Thus, our data indicate that PDZD8 is a shared component of two distinct MCSs and suggest a role for SMP-mediated lipid transport in the regulation of endosome function. Membrane contact sites between organelles have been shown to play important biological roles. Here, the authors show that at the ER, PDZD8 associates with Protrudin and also with Rab7 endosomes and recruits mitochondria to form three-way contacts.