Department of Biology, Queens College, Flushing, NY, USA.
Autophagy. 2011 Apr;7(4):386-400. doi: 10.4161/auto.7.4.14391. Epub 2011 Apr 1.
Autophagy and endocytosis are dynamic and tightly regulated processes that contribute to many fundamental aspects of biology including survival, longevity, and development. However, the molecular links between autophagy and endocytosis are not well understood. Here, we report that BEC-1, the C. elegans ortholog of Atg6/Vps30/Beclin1, a key regulator of the autophagic machinery, also contributes to endosome function. In particular we identify a defect in retrograde transport from endosomes to the Golgi in bec-1 mutants. MIG-14/Wntless is normally recycled from endosomes to the Golgi through the action of the retromer complex and its associated factor RME-8. Lack of retromer or RME-8 activity results in the aberrant transport of MIG-14/Wntless to the lysosome where it is degraded. Similarly, we find that lack of bec-1 also results in mislocalization and degradation of MIG-14::GFP, reduced levels of RME-8 on endosomal membranes, and the accumulation of morphologically abnormal endosomes. A similar phenotype was observed in animals treated with dsRNA against vps-34. We further identify a requirement for BEC-1 in the clearance of apoptotic corpses in the hermaphrodite gonad, suggesting a role for BEC-1 in phagosome maturation, a process that appears to depend upon retrograde transport. In addition, autophagy genes may also be required for cell corpse clearance, as we find that RNAi against atg-18 or unc-51 also results in a lack of cell corpse clearance.
自噬和内吞作用是动态且受到严格调控的过程,它们对包括生存、长寿和发育在内的生物学的许多基本方面都有贡献。然而,自噬和内吞作用之间的分子联系还没有得到很好的理解。在这里,我们报告说,BEC-1,秀丽隐杆线虫 Atg6/Vps30/Beclin1 的同源物,是自噬机制的关键调节因子,也有助于内体功能。特别是,我们发现 bec-1 突变体在内体到高尔基体的逆行运输中存在缺陷。MIG-14/Wntless 通常通过 retromer 复合物及其相关因子 RME-8 的作用从内体循环到高尔基体。缺乏 retromer 或 RME-8 的活性会导致 MIG-14/Wntless 异常运输到溶酶体,在那里被降解。同样,我们发现缺乏 bec-1 也会导致 MIG-14::GFP 的定位和降解,内体膜上的 RME-8 水平降低,以及形态异常的内体积累。在针对 vps-34 的 dsRNA 处理的动物中观察到类似的表型。我们进一步确定 BEC-1 在雌雄同体性腺中清除凋亡细胞的尸体中是必需的,这表明 BEC-1 在吞噬体成熟中发挥作用,这一过程似乎依赖于逆行运输。此外,自噬基因也可能是细胞尸体清除所必需的,因为我们发现针对 atg-18 或 unc-51 的 RNAi 也会导致细胞尸体清除的缺乏。