Exomer complex regulates protein traffic at the TGN through differential interactions with cargos and clathrin adaptor complexes.
Exomer complex regulates protein traffic at the TGN through differential interactions with cargos and clathrin adaptor complexes.
复制标题
DOI：
10.1096/fj.202002610r
复制
发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
在反式高尔基体网络（TGN）的蛋白质分选通常需要货物衔接子的帮助。然而，还有待研究的是，相同的复合物如何介导不同蛋白质的输出和保留，或者分选复合物如何相互作用。在酿酒酵母（Saccharomyces cerevisiae）中，外消旋体复合物参与了一些蛋白质从TGN到质膜（PM）的极化转运。有趣的是，外消旋体及其货物也显示出与TGN网格蛋白衔接子的一种功能关系，这仍然是未解决的。在这里，使用广泛的技术，包括延时和BIFC显微镜，我们描述了新的外消旋体复合物在蛋白质分选的分子意义，并解决其不同层的功能相互作用与网格蛋白适配器复合物。外聚体突变体显示受损的氨基酸摄取，因为它不仅有利于极化的氨基酸渗透酶的PM，但也参与其内体交通。我们提出了一个模型外消旋体，它直接或间接地通过Arf 1功能调节TGN网格蛋白衔接子的招聘。此外，我们描述了模型货物Chs 3的外消旋体和AP-1复合物之间的体内竞争关系。这些结果突出了外消旋体在调节TGN蛋白分选中的广泛作用，这与其作为货物衔接子的作用是互补的，并提出了一个模型来理解TGN蛋白分选的复杂性。
Protein sorting at the trans Golgi network (TGN) usually requires the assistance of cargo adaptors. However, it remains to be examined how the same complex can mediate both the export and retention of different proteins or how sorting complexes interact among themselves. In Saccharomyces cerevisiae, the exomer complex is involved in the polarized transport of some proteins from the TGN to the plasma membrane (PM). Intriguingly, exomer and its cargos also show a sort of functional relationship with TGN clathrin adaptors that is still unsolved. Here, using a wide range of techniques, including time-lapse and BIFC microscopy, we describe new molecular implications of the exomer complex in protein sorting and address its different layers of functional interaction with clathrin adaptor complexes. Exomer mutants show impaired amino acid uptake because it facilitates not only the polarized delivery of amino acid permeases to the PM but also participates in their endosomal traffic. We propose a model for exomer where it modulates the recruitment of TGN clathrin adaptors directly or indirectly through Arf1 function. Moreover, we describe an in vivo competitive relationship between the exomer and AP-1 complexes for the model cargo Chs3. These results highlight a broad role for exomer in regulating protein sorting at the TGN that is complementary to its role as cargo adaptor and present a model to understand the complexity of TGN protein sorting.
影响因子：
5.5
作者：
Weiskoff AM;Fromme JC
通讯作者：
Fromme JC