Ubiquitin binding and conjugation regulate the recruitment of Rabex-5 to early endosomes
Ubiquitin binding and conjugation regulate the recruitment of Rabex-5 to early endosomes
复制标题
DOI：
10.1038/emboj.2008.177
复制
发表时间：
2008-10-08
期刊：
影响因子：
11.4
通讯作者：
Bonifacino, Juan S.
中科院分区：
文献类型：
--
作者：
Mattera, Rafael;Bonifacino, Juan S.
Rab GTP 酶和泛素化是内吞和溶酶体靶向途径中跨膜货物分选的关键调节因子。内体蛋白 Rabex-5 既是 Rab5 的鸟嘌呤核苷酸交换因子 (GEF)，又是泛素 (Ub) 结合和缀合的底物，从而贯穿这两层调控。众所周知，运输机械部件结合泛素化蛋白质的能力在货物分拣中具有功能。在这里，我们证明 Ub 结合对于将 Rabex-5 从胞质溶胶招募到内体至关重要，独立于其 GEF 活性和 Rab5。我们还表明单泛素化的 Rabex-5 在细胞质中富集。这些观察结果与 Ub 结合和单泛素化循环调节 Rabex-5 与内体关联的模型一致。
Rab GTPases and ubiquitination are critical regulators of transmembrane cargo sorting in endocytic and lysosomal targeting pathways. The endosomal protein Rabex-5 intersects these two layers of regulation by being both a guanine nucleotide exchange factor (GEF) for Rab5 and a substrate for ubiquitin (Ub) binding and conjugation. The ability of trafficking machinery components to bind ubiquitinated proteins is known to have a function in cargo sorting. Here, we demonstrate that Ub binding is essential for the recruitment of Rabex-5 from the cytosol to endosomes, independently of its GEF activity and of Rab5. We also show that monoubiquitinated Rabex-5 is enriched in the cytosol. These observations are consistent with a model whereby a cycle of Ub binding and monoubiquitination regulates the association of Rabex-5 with endosomes.