The RAB GTPase RAB18 modulates macroautophagy and proteostasis
The RAB GTPase RAB18 modulates macroautophagy and proteostasis
复制标题
DOI：
10.1016/j.bbrc.2017.03.112
复制
发表时间：
2017-05-06
影响因子：
3.1
通讯作者：
Kern, Andreas
中科院分区：
文献类型：
--
作者：
Feldmann, Anne;Bekbulat, Fazilet;Kern, Andreas
大细胞自噬是一种保守的降解途径，其恶化与细胞蛋白质稳态紊乱和多种疾病有关。在这里，我们表明，RAB GT3 RAB 18调节原代人成纤维细胞中的自噬。RAB 18的敲低导致自噬活性降低，而其过表达增强降解途径。重要的是，RAB 18的这种功能依赖于RAB 3GAP 1和RAB 3GAP 2，它们可能充当RAB GEF并刺激RAB GT3的活性。此外，RAB 18的敲低使蛋白质稳态恶化，并导致泛素化降解倾向蛋白的细胞内积累。因此，RAB GT3-RAB 18是自噬的正调节剂，并且与细胞蛋白质稳态的维持相关。(C)2017作者爱思唯尔公司出版
Macroautophagy is a conserved degradative pathway and its deterioration is linked to disturbances in cellular proteostasis and multiple diseases. Here, we show that the RAB GTPase RAB18 modulates autophagy in primary human fibroblasts. The knockdown of RAB18 results in a decreased autophagic activity, while its overexpression enhances the degradative pathway. Importantly, this function of RAB18 is dependent on RAB3GAP1 and RAB3GAP2, which might act as RAB GEFs and stimulate the activity of the RAB GTPase. Moreover, the knockdown of RAB18 deteriorates proteostasis and results in the intracellular accumulation of ubiquitinated degradation-prone proteins. Thus, the RAB GTPase RAB18 is a positive modulator of autophagy and is relevant for the maintenance of cellular proteostasis. (C) 2017 The Authors. Published by Elsevier Inc.