Aikawa Yoshikatsu, Lee Sangho
Laboratory of Neural Membrane Biology; Graduate School of Brain Science; Doshisha University; Kyoto, Japan.
Commun Integr Biol. 2013 Jul 1;6(4):e24463. doi: 10.4161/cib.24463. Epub 2013 Apr 9.
The covalent modification of transmembrane receptors by ubiquitin (Ub) is a key biological mechanism controlling their internalization and endocytic sorting to recycling and degradative pathways to attenuate their signaling potential. In this Ub-dependent endocytic trafficking pathway, Ub-binding proteins (UBPs) play a critical role in the sorting of these ubiquitinated transmembrane proteins at the plasma membrane, early endosomes, and multivesicular bodies. We recently reported that Rabex-5, a UBP and guanine nucleotide exchange factor for Rab5, is translocated to the plasma membrane in an extracellular ligand-dependent manner to regulate the internalization of ligand-induced ubiquitinated transmembrane proteins upon stimulation with extracellular ligands. Here, we show that Rabex-5 predominantly localizes on Rab5- and syntaxin 13-positive endosomes, but not on Rab11-positive recycling endosomes before stimulation with extracellular ligands. We further discuss the significance of Rabex-5-mediated sorting of ubiquitinated transmembrane proteins as cargo at an early stage of the endocytic pathway.
泛素（Ub）对跨膜受体的共价修饰是一种关键的生物学机制，可控制其内化以及通过内吞分选进入再循环和降解途径，从而减弱其信号传导潜力。在这条依赖泛素的内吞运输途径中，泛素结合蛋白（UBP）在这些泛素化跨膜蛋白于质膜、早期内体和多囊泡体中的分选过程中发挥着关键作用。我们最近报道，Rabex-5作为一种UBP和Rab5的鸟嘌呤核苷酸交换因子，在细胞外配体的刺激下，以细胞外配体依赖的方式转运至质膜，以调节配体诱导的泛素化跨膜蛋白的内化。在此，我们表明，在细胞外配体刺激之前，Rabex-5主要定位于Rab5和 syntaxin 13阳性的内体上，而不是Rab11阳性的再循环内体上。我们进一步讨论了Rabex-5介导的泛素化跨膜蛋白作为内吞途径早期货物的分选意义。
