Monoubiquitination of EEA1 regulates endosome fusion and trafficking.
Monoubiquitination of EEA1 regulates endosome fusion and trafficking.
复制标题
DOI：
10.1186/2045-3701-3-24
复制
发表时间：
2013-05-23
影响因子：
7.5
通讯作者：
Ye Y
中科院分区：
文献类型：
--
作者：
Ramanathan HN;Zhang G;Ye Y
早期内小体自身抗原1(EEA1)是内吞作用中早期内小体融合和成熟所必需的膜系留因子。EEA1的活性在细胞中是如何调节的还不清楚。在这里，我们表明，内源性EEA1容易在多个位置发生单泛素化，这是由于它与泛素结合酶(E2)具有内在的亲和力。E2相互作用使泛素连接酶(E3)不依赖于机制，用多个单一泛素部分装饰EEA1。泛素-EEA1嵌合体的表达模仿了天然的单一泛素化的EEA1，产生了与细胞核毗邻的巨大内体。一些证据表明，这种表型是由于内小体融合增加和内小体循环途径同时受阻所致。后者可能是由于表达泛素-EEA1的细胞内内体分裂减少所致。我们的结果表明，泛素化可能显著影响内体融合因子的活性，从而改变内体的形态和运输模式，从而暗示泛素信号在内吞作用中发挥了意想不到的作用。
Early endosomal autoantigen 1 (EEA1) is a membrane tethering factor required for the fusion and maturation of early endosomes in endocytosis. How the activity of EEA1 is regulated in cells is unclear. Here we show that endogenous EEA1 is prone to monoubiquitination at multiple sites, owing to an intrinsic affinity to ubiquitin conjugating enzymes (E2). The E2 interactions enable a ubiquitin ligase (E3) independent mechanism that decorate EEA1 with multiple mono-ubiquitin moieties. Expression of an ubiquitin-EEA1 chimera that mimics native mono-ubiquitinated EEA1 generates giant endosomes abutting the nucleus. Several lines of evidence suggest that this phenotype is due to increased endosome fusion and a simultaneous blockade on an endosome recycling pathway. The latter is likely caused by diminished endosome fission in cells expressing ubiquitin-EEA1. Our results demonstrate that ubiquitination may dramatically affect the activity of an endosome fusion factor to alter endosome morphology and trafficking pattern, and thereby implicating an unexpected role of ubiquitin signaling in endocytosis.
登录
查看更多内容
影响因子：
64.5
作者：
Katzmann, DJ;Babst, M;Emr, SD
通讯作者：
Emr, SD
影响因子：
64.8
作者：
Li, Wei;Tu, Daqi;Ye, Yihong
通讯作者：
Ye, Yihong
影响因子：
3.3
作者：
Mizuno, E;Iura, T;Komada, M
通讯作者：
Komada, M
影响因子：
64.5
作者：
McBride, HM;Rybin, V;Zerial, M
通讯作者：
Zerial, M
影响因子：
11.4
作者：
Braun, S;Matuschewski, K;Jentsch, S
通讯作者：
Jentsch, S