Bro1 coordinates deubiquitination in the multivesicular body pathway by recruiting Doa4 to endosomes.
Bro1 coordinates deubiquitination in the multivesicular body pathway by recruiting Doa4 to endosomes.
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BRO1通过将DOA4募集到内体中，在多囊体途径中进行去泛素化。
DOI：
10.1083/jcb.200403139
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发表时间：
2004-08-30
影响因子：
7.8
通讯作者：
Odorizzi, Greg
中科院分区：
文献类型：
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作者：
Luhtala, Natalie;Odorizzi, Greg
泛素化指导细胞表面受体和其他整体膜蛋白的分选进入多泡体（MVB）途径。随后，货物蛋白在被包裹在MVB囊泡内之前被去泛素化。在酿酒酵母中，Bro1在MVB分选的后期起作用，是货物蛋白去泛素化所必需的。我们发现Bro1功能的丧失受到DOA4过表达的抑制，DOA4编码从MVB货物中去除泛素所需的泛素硫酯酶。DOA4的过表达通过MVB途径恢复了货物蛋白的去泛素化和分选，并逆转了bro1突变细胞典型的异常内体形态，导致多泡内体的恢复。我们进一步证明Doa4与内体膜上的Bro1相互作用，并且Doa4向内体募集需要Bro1。因此，我们的研究结果表明Bro1在MVB通路中协调Doa4去泛素化的时间和位置方面发挥了关键作用。
Ubiquitination directs the sorting of cell surface receptors and other integral membrane proteins into the multivesicular body (MVB) pathway. Cargo proteins are subsequently deubiquitinated before their enclosure within MVB vesicles. In Saccharomyces cerevisiae, Bro1 functions at a late step of MVB sorting and is required for cargo protein deubiquitination. We show that the loss of Bro1 function is suppressed by the overexpression of DOA4, which encodes the ubiquitin thiolesterase required for the removal of ubiquitin from MVB cargoes. Overexpression of DOA4 restores cargo protein deubiquitination and sorting via the MVB pathway and reverses the abnormal endosomal morphology typical of bro1 mutant cells, resulting in the restoration of multivesicular endosomes. We further demonstrate that Doa4 interacts with Bro1 on endosomal membranes and that the recruitment of Doa4 to endosomes requires Bro1. Thus, our results point to a key role for Bro1 in coordinating the timing and location of deubiquitination by Doa4 in the MVB pathway.