His domain protein tyrosine phosphatase and Rabaptin-5 couple endo-lysosomal sorting of EGFR with endosomal maturation.
His domain protein tyrosine phosphatase and Rabaptin-5 couple endo-lysosomal sorting of EGFR with endosomal maturation.
复制标题
DOI：
10.1242/jcs.259192
复制
发表时间：
2021-11-01
影响因子：
4
通讯作者：
Woodman P
中科院分区：
文献类型：
--
作者：
Parkinson G;Roboti P;Zhang L;Taylor S;Woodman P
His结构域蛋白酪氨酸磷酸酶(HD-PTP；也称为PTPN23)与转运所需的内体分选复合体(ESCRT)合作，将内体货物分拣到腔内小泡中，形成多囊泡体(MVB)。MVB分选的完成伴随着内体成熟为晚期内体，这一事件需要失活早期内体GTP酶Rab5(这里泛指所有异构体)。在这里，我们证明了HD-PTP将ESCRT功能与内体成熟联系起来。HD-PTP的耗尽阻止了MVB的分选，同时也阻止了货物离开富含Rab5的内体。HD-PTP缺失的细胞含有过度磷酸化的Rabaptin-5(也称为RABEP1)，这是Rab5鸟嘌呤核苷酸交换因子Rabex-5(也称为RABGEF1)的辅助因子，尽管HD-PTP不太可能直接去磷酸化Rabaptin-5。此外，HD-PTP缺失的细胞表现出Rabaptin-5依赖的Rab5的过度激活。HD-PTP直接与Rabaptin-5结合，位于其Rabex-5和Rab5结合区之间。这种结合反应涉及HD-PTP中的ESCRT-0/ESCRT-III结合位点，该结合位点被ESCRT-III肽竞争。这些发现共同表明，HD-PTP可能作为ESCRT的支架，调节Rabex-5-Rabaptin-5的活性，从而帮助协调MVB分选的完成和内体成熟。摘要：胞内货物分选到多囊泡体伴随着胞体成熟。在这里，我们提供了一种潜在的机制，通过它将这两个过程联系在一起。
His domain protein tyrosine phosphatase (HD-PTP; also known as PTPN23) collaborates with endosomal sorting complexes required for transport (ESCRTs) to sort endosomal cargo into intralumenal vesicles, forming the multivesicular body (MVB). Completion of MVB sorting is accompanied by maturation of the endosome into a late endosome, an event that requires inactivation of the early endosomal GTPase Rab5 (herein referring to generically to all isoforms). Here, we show that HD-PTP links ESCRT function with endosomal maturation. HD-PTP depletion prevents MVB sorting, while also blocking cargo from exiting Rab5-rich endosomes. HD-PTP-depleted cells contain hyperphosphorylated Rabaptin-5 (also known as RABEP1), a cofactor for the Rab5 guanine nucleotide exchange factor Rabex-5 (also known as RABGEF1), although HD-PTP is unlikely to directly dephosphorylate Rabaptin-5. In addition, HD-PTP-depleted cells exhibit Rabaptin-5-dependent hyperactivation of Rab5. HD-PTP binds directly to Rabaptin-5, between its Rabex-5- and Rab5-binding domains. This binding reaction involves the ESCRT-0/ESCRT-III binding site in HD-PTP, which is competed for by an ESCRT-III peptide. Jointly, these findings indicate that HD-PTP may alternatively scaffold ESCRTs and modulate Rabex-5–Rabaptin-5 activity, thereby helping to coordinate the completion of MVB sorting with endosomal maturation. Summary: Sorting of endocytic cargo to the multivesicular body is accompanied by endosomal maturation. Here, we provide a potential mechanism by which these two processes are linked.
登录
查看更多内容
影响因子：
64.5
作者：
Horiuchi, H;Lippe, R;Zerial, M
通讯作者：
Zerial, M
DOI：
10.1111/j.1600-0854.2011.01305.x
发表时间：
2012-02
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Eden ER;Huang F;Sorkin A;Futter CE
通讯作者：
Futter CE
DOI：
10.1083/jcb.201110031
发表时间：
2012-04-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dores MR;Chen B;Lin H;Soh UJ;Paing MM;Montagne WA;Meerloo T;Trejo J
通讯作者：
Trejo J
影响因子：
11.8
作者：
Christoforides, Claudine;Rainero, Elena;Brown, Kristin K.;Norman, Jim C.;Toker, Alex
通讯作者：
Toker, Alex
影响因子：
56.9
作者：
Carlton, Jez G.;Martin-Serrano, Juan
通讯作者：
Martin-Serrano, Juan