Falguières Thomas, Luyet Pierre-Philippe, Gruenberg Jean
Department of Biochemistry, University of Geneva, 30 quai Ernest Ansermet-1211 Geneva 4, Switzerland.
Exp Cell Res. 2009 May 15;315(9):1567-73. doi: 10.1016/j.yexcr.2008.12.006. Epub 2008 Dec 24.
Along the degradation pathway, endosomes exhibit a characteristic multivesicular organization, resulting from the budding of vesicles into the endosomal lumen. After endocytosis and transport to early endosomes, activated signaling receptors are incorporated into these intralumenal vesicles through the action of the ESCRT machinery, a process that contributes to terminate signaling. Then, the vesicles and their protein cargo are further transported towards lysosomes for degradation. Evidence also shows that intralumenal vesicles can undergo "back-fusion" with the late endosome limiting membrane, a route exploited by some pathogens and presumably followed by proteins and lipids that need to be recycled from within the endosomal lumen. This process depends on the late endosomal lipid lysobisphosphatidic acid and its putative effector Alix/AIP1, and is presumably coupled to the invagination of the endosomal limiting membrane at the molecular level via ESCRT proteins. In this review, we discuss the intra-endosomal transport routes in mammalian cells, and in particular the different mechanisms involved in membrane invagination, vesicle formation and fusion in a space inaccessible to proteins known to control intracellular membrane traffic.
在内吞体降解途径中，内吞体呈现出一种典型的多囊泡结构，这是由小泡出芽进入内吞体腔形成的。内吞作用发生并将物质转运至早期内吞体后，活化的信号受体通过内体分选转运复合体（ESCRT）机制的作用被纳入这些腔内小泡，这一过程有助于终止信号传导。然后，这些小泡及其蛋白质货物被进一步转运至溶酶体进行降解。有证据还表明，腔内小泡可与晚期内吞体限制膜发生“反向融合”，一些病原体利用这一途径，可能需要从内吞体腔内循环利用的蛋白质和脂质也会遵循这一途径。这一过程依赖于晚期内吞体脂质双磷酸磷脂酸及其假定效应物Alix/AIP1，并且可能在分子水平上通过ESCRT蛋白与内吞体限制膜的内陷相偶联。在本综述中，我们讨论了哺乳动物细胞内的内吞体运输途径，特别是在已知控制细胞内膜运输的蛋白质无法进入的空间中，膜内陷、小泡形成和融合所涉及的不同机制。
