ESCRT proteins, endosome organization and mitogenic receptor down-regulation.

ESCRT proteins, endosome organization and mitogenic receptor down-regulation.
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ESCRT 蛋白、内体组织和促有丝分裂受体下调。

DOI:
10.1042/bst0370146
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发表时间:
2009
影响因子:
3.9
通讯作者:
Woodman P
Woodman P
中科院分区:
生物学3区
文献类型:
--
作者:
Woodman P

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有丝分裂性酪氨酸激酶受体,如表皮生长因子受体,一旦在细胞表面被激活,就会被内吞。在到达早期核内体后,它们在其细胞质结构域内被泛素化,并因此从循环受体中分离出来。然后它们被合并到MVB(多泡体)的腔内囊泡中,在到达溶酶体的途中被降解。MVB的形成需要早期核内体液泡结构域的稳定,降解货物在该结构域中的分离(随后将受体如EGFR并入腔内囊泡),以及该结构域从早期核内体管状区域的物理分离和移动。MVB生物发生的这些不同方面是如何耦合的尚不清楚,但escrt(运输所需的内体分选复合物)已被确定为驱动有丝分裂受体隔离和腔内囊泡形成的关键分子。本综述总结了该领域和我们实验室关于escrt和相关蛋白在驱动EGFR泛素依赖性分选和维持早期内体结构域组织中的详细功能的最新发现。
Mitogenic tyrosine kinase receptors such as the EGFR (epidermal growth factor receptor) are endocytosed once they are activated at the cell surface. After reaching the early endosome, they are ubiquitinated within their cytosolic domain and are consequently sorted away from recycling receptors. They are then incorporated into intraluminal vesicles within the MVB (multivesicular body) en route to the lysosome, where they are degraded. MVB formation requires the stabilization of the vacuolar domain of the early endosome, the segregation of degradative cargo within this domain (with subsequent incorporation of receptors such as EGFR into intraluminal vesicles) and the physical separation and movement of this domain away from the tubular regions of the early endosome. How these different aspects of MVB biogenesis are coupled is unknown, but ESCRTs (endosomal sorting complexes required for transport) have been identified as key molecular players in driving mitogenic receptor sequestration and formation of intraluminal vesicles. The present review summarizes recent findings within the field and from our laboratory regarding the detailed function of ESCRTs and associated proteins in driving the ubiquitin-dependent sorting of EGFR and in maintaining the domain organization of the early endosome.
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