Monoubiquitination of Syntaxin 5 Regulates Golgi Membrane Dynamics during the Cell Cycle.
Monoubiquitination of Syntaxin 5 Regulates Golgi Membrane Dynamics during the Cell Cycle.
复制标题
语法5的单泛素化调节细胞周期中的高尔基膜动力学。
DOI：
10.1016/j.devcel.2016.06.001
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发表时间：
2016-07-11
影响因子：
11.8
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Huang S;Tang D;Wang Y
高尔基体在细胞分裂的每个周期都经历一个依赖于泛素的分解和重组过程。在这里，我们报告的高尔基体t-SNARE syntaxin 5（Syn 5）作为泛素化底物的鉴定。Syn 5在有丝分裂早期被泛素连接酶HACE 1单泛素化，在有丝分裂晚期被去泛素化酶VCIP 135去泛素化。SNARE结构域中赖氨酸270（K270）上的Syn 5泛素化损害了Syn 5与同源v-SNARE Bet 1之间的相互作用，但增加了其与p97的衔接蛋白p47的结合。Syn 5 K270 R突变体在细胞中的表达损害有丝分裂后高尔基体的重组。因此，Syn 5在有丝分裂早期的单泛素化破坏了SNARE复合物的形成。随后，泛素化的Syn 5招募p97/p47到有丝分裂的高尔基体片段，并促进有丝分裂后的高尔基体重组泛素去除VCIP 135。总之，这项研究揭示了底物和泛素介导的调节高尔基体膜动力学在细胞周期中的机制。高尔基体在细胞周期中经历泛素依赖的拆卸和重新组装。Huang等鉴定Syntaxin 5（Syn 5）为高尔基体上的泛素化底物。他们表明，通过HACE 1的Syn 5泛素化和通过VCIP 135的去泛素化，调节Syn 5与高尔基体组装中涉及的蛋白质的相互作用，从而调节它们的募集。
The Golgi apparatus undergoes a ubiquitin-dependent disassembly and reassembly process during each cycle of cell division. Here we report the identification of the Golgi t-SNARE syntaxin 5 (Syn5) as the ubiquitinated substrate. Syn5 is monoubiquitinated by the ubiquitin ligase HACE1 in early mitosis and deubiquitinated by the deubiquitinase VCIP135 in late mitosis. Syn5 ubiquitination on Lysine 270 (K270) in the SNARE domain impairs the interaction between Syn5 and the cognate v-SNARE Bet1, but increases its binding to p47, the adaptor protein of p97. Expression of the Syn5 K270R mutant in cells impairs post-mitotic Golgi reassembly. Therefore, monoubiquitination of Syn5 in early mitosis disrupts SNARE complex formation. Subsequently, ubiquitinated Syn5 recruits p97/p47 to the mitotic Golgi fragments and promotes post-mitotic Golgi reassembly upon ubiquitin removal by VCIP135. Overall, this study reveals both the substrate and the mechanism of ubiquitin-mediated regulation of Golgi membrane dynamics during the cell cycle. The Golgi undergoes ubiquitin-dependent disassembly and reassembly during the cell cycle. Huang et al. identify Syntaxin 5 (Syn5) as the ubiquitinated substrate on the Golgi. They show that Syn5 ubiquitination by HACE1, and deubiquitination by VCIP135, regulate Syn5 interactions with, and hence recruitment of, proteins involved in Golgi assembly.