Rab4 affects both recycling and degradative endosomal trafficking
Rab4 affects both recycling and degradative endosomal trafficking
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DOI：
10.1016/s0014-5793(01)02359-6
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发表时间：
2001-04-20
期刊：
影响因子：
3.5
通讯作者：
Bucci, C
中科院分区：
文献类型：
--
作者：
McCaffrey, MW;Bielli, A;Bucci, C
小 GTPases Rab4、Rab5 和 Rab7 是内体蛋白，在内体运输的各个阶段的调节中发挥重要作用，Rab4 和 Rab5 均定位于早期内体，并已被证明分别控制再循环和内体融合。 Rab7 是晚期内体区室的标记物，参与晚期内吞途径的调节。在这里，我们比较了 Rab4、Rab5 和 Rab7 在 HeLa 细胞早期和晚期内体运输中的作用，监测配体的摄取、回收和降解。 Rab4 显性失活突变体 (Rab4AS22N) 的表达导致回收和降解显着减少，而正如预期的那样，Rab7 突变体专门影响表皮生长因子 (EGF) 和低密度脂蛋白降解。正如预期的那样，显性失活 Rab5 突变体的表达扰乱了内化动力学；并影响回收和降解。 Rab4WT 和显性阳性突变体 (Rab4AQ67L) 的表达显着改变转铁蛋白区室的形态，导致膜小管的形成，这些转铁蛋白阳性小管表现出肿胀（静脉曲张），其中一些对早期内体抗原 1 呈阳性并含有 EGF。我们认为 Rab4GTPase 对于早期分选内体的功能很重要 隔室，影响沿回收和降解途径的贩运。 (C) 2001 年欧洲生化学会联合会。由 Elsevier Science B.V. 出版。保留所有权利。
The small GTPases Rab4, Rab5 and Rab7 are endosomal proteins which play important roles in the regulation of various stages of endosomal trafficking, Rab4 and Rab5 have both been localized to early endosomes and ha,e been shown to control recycling and endosomal fusion, respectively. Rab7, a marker of the late endosomal compartment, is involved in the regulation of the late endocytic pathway. Here, we compare the role of Rab4, Rab5 and Rab7 in early and late endosomal trafficking in HeLa cells monitoring ligand uptake, recycling and degradation. Expression of the Rab4 dominant negative mutant (Rab4AS22N) leads to a significant reduction in both recycling and degradation while, as expected, Rab7 mutants exclusively affect epidermal growth factor (EGF) and low density lipoprotein degradation. As also expected, expression of the dominant negative Rab5 mutant perturbs internalization kinetics; and affects both recycling and degradation. Expression of Rab4WT and dominant positive mutant (Rab4AQ67L) changes dramatically the morphology of the transferrin compartment leading to the formation of membrane tubulus, These transferrin positive tubules display swellings (varicosities) some of which are positive for early endosomal antigen-1 and contain EGF, We propose that the Rab4GTPase is important for the function of the early sorting endosomal compartment, affecting trafficking along both recycling and degradative pathways. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.