UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting
UBAP1 Is a Component of an Endosome-Specific ESCRT-I Complex that Is Essential for MVB Sorting
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DOI：
10.1016/j.cub.2011.06.028
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发表时间：
2011-07-26
期刊：
影响因子：
9.2
通讯作者：
Woodman, Philip
中科院分区：
文献类型：
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作者：
Stefani, Flavia;Zhang, Ling;Woodman, Philip
转运所需的内体分选复合物（ESCRT）调节涉及膜内陷的几个事件，包括多泡体（MVB）生物发生、病毒出芽和胞质分裂[1]。在每种情况下，上游ESCRT联合收割机与其他因子（如Bro 1蛋白[2-4]）结合，以募集ESCRT-III和ATP酶VPS 4，从而驱动膜断裂[5]。理解这些不同的细胞过程如何相互独立地控制的一个线索是ESCRT亚型的鉴定。哺乳动物ESCRT-I包括TSG 101、VPS 28、VPS 37 A-D [6-8]和MVB 12 A/B [9]。这些可以产生几种ESCRT-I复合物，每种复合物都靶向不同的隔室，并且能够招募不同的ESCRT-III蛋白。在这里，我们鉴定了一种新的ESCRT-I组分，泛素相关蛋白1（UBAP 1），它含有MVB 12中保守的区域[10]。UBAP 1结合内体Bro 1蛋白His结构域蛋白酪氨酸磷酸酶（HDPTP）[4]，但不结合阿利克斯（一种参与胞质分裂的Bro 1蛋白）[11，12]。UBAP 1是将EGFR分选到MVB和内体泛素稳态所需的，但不是胞质分裂所需的。UBAP 1是一种复合物的一部分，该复合物含有总细胞TSG 101的一部分，并且还含有VPS 37 A，但不含有VPS 37 C。因此，UBAP 1的存在与VPS 37 A的组合定义了内体特异性ESCRT-1复合物。
Endosomal sorting complexes required for transport (ESCRTs) regulate several events involving membrane invagination, including multivesicular body (MVB) biogenesis, viral budding, and cytokinesis [1]. In each case, upstream ESCRTs combine with additional factors, such as Bro1 proteins [2-4], to recruit ESCRT-III and the ATPase VPS4 in order to drive membrane scission [5]. A clue to understanding how such diverse cellular processes might be controlled independently of each other has been the identification of ESCRT isoforms. Mammalian ESCRT-I comprises TSG101, VPS28, VPS37A-D [6-8], and MVB12A/B [9]. These could generate several ESCRT-I complexes, each targeted to a different compartment and able to recruit distinct ESCRT-III proteins. Here we identify a novel ESCRT-I component, ubiquitin-associated protein 1 (UBAP1), which contains a region conserved in MVB12 [10]. UBAP1 binds the endosomal Bro1 protein His domain protein tyrosine phosphatase (HDPTP) [4], but not Alix, a Bro1 protein involved in cytokinesis [11,12]. UBAP1 is required for sorting EGFR to the MVB and for endosomal ubiquitin homeostasis, but not for cytokinesis. UBAP1 is part of a complex that contains a fraction of total cellular TSG101 and that also contains VPS37A but not VPS37C. Hence, the presence of UBAP1, in combination with VPS37A, defines an endosome-specific ESCRT-I complex.