Department of Cell Biology, Yale School of Medicine, New Haven, CT 06520.
J Cell Biol. 2014 Mar 3;204(5):793-806. doi: 10.1083/jcb.201309084. Epub 2014 Feb 24.
Retromer is an endosomal sorting device that orchestrates capture and packaging of cargo into transport carriers coated with sorting nexin BAR domain proteins (SNX-BARs). We report that fission of retromer SNX-BAR-coated tubules from yeast endosomes is promoted by Vps1, a dynamin-related protein that localizes to endosomes decorated by retromer SNX-BARs and Mvp1, a SNX-BAR that is homologous to human SNX8. Mvp1 exhibits potent membrane remodeling activity in vitro, and it promotes association of Vps1 with the endosome in vivo. Retrograde transport carriers bud from the endosome coated by retromer and Mvp1, and cargo export is deficient in mvp1- and vps1-null cells, but with distinct endpoints; cargo export is delayed in mvp1-null cells, but cargo export completely fails in vps1-null cells. The results indicate that Mvp1 promotes Vps1-mediated fission of retromer- and Mvp1-coated tubules that bud from the endosome, revealing a functional link between the endosomal sorting and fission machineries to produce retrograde transport carriers.
Retromer 是一种内体分拣装置，它协调捕获和将货物包装到由分选连接蛋白 BAR 结构域蛋白 (SNX-BARs) 包裹的运输载体中。我们报告说，酵母内体中 retromer SNX-BAR 包裹的小管的裂变是由 Vps1 促进的，Vps1 是一种与 retromer SNX-BAR 和 Mvp1 定位在内体的动力相关蛋白，Mvp1 是一种与人类 SNX8 同源的 SNX-BAR。Mvp1 在体外具有很强的膜重塑活性，并促进 Vps1 与内体的体内结合。逆行运输载体从 retromer 和 Mvp1 包被的内体上芽生，mvp1 和 vps1 缺失细胞中货物出口缺陷，但终点不同；mvp1 缺失细胞中货物出口延迟，但 vps1 缺失细胞中货物出口完全失败。结果表明，Mvp1 促进 retromer 和 Mvp1 包被的小管的 Vps1 介导的裂变，该小管从内体上芽生，揭示了内体分拣和裂变机制之间的功能联系，以产生逆行运输载体。
