SNX32 Regulates Sorting and Trafficking of Activated EGFR to the Lysosomal Degradation Pathway.

IF 3.6 3区生物学 Q3 CELL BIOLOGY Traffic Pub Date : 2024-07-01 DOI:10.1111/tra.12952

Dou Wang, Xia Zhao, Panpan Wang, Jia-Jia Liu

引用次数: 0

Abstract

SNX32 is a member of the evolutionarily conserved Phox (PX) homology domain- and Bin/Amphiphysin/Rvs (BAR) domain- containing sorting nexin (SNX-BAR) family of proteins, which play important roles in sorting and membrane trafficking of endosomal cargoes. Although SNX32 shares the highest amino acid sequence homology with SNX6, and has been believed to function redundantly with SNX5 and SNX6 in retrieval of the cation-independent mannose-6-phosphate receptor (CI-MPR) from endosomes to the trans-Golgi network (TGN), its role(s) in intracellular protein trafficking remains largely unexplored. Here, we report that it functions in parallel with SNX1 in mediating epidermal growth factor (EGF)-stimulated postendocytic trafficking of the epidermal growth factor receptor (EGFR). Moreover, SNX32 interacts directly with EGFR, and recruits SNX5 to promote sorting of EGF-EGFR into multivesicular bodies (MVBs) for lysosomal degradation. Thus, SNX32 functions distinctively from other SNX-BAR proteins to mediate signaling-coupled endolysosomal trafficking of EGFR.

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SNX32 调控活化表皮生长因子受体向溶酶体降解途径的排序和迁移

SNX32是进化保守的含Phox（PX）同源结构域和Bin/Amphiphysin/Rvs（BAR）结构域的分选神经蛋白（SNX-BAR）家族的成员，在内体货物的分选和膜贩运中发挥着重要作用。尽管SNX32与SNX6的氨基酸序列同源性最高，而且被认为与SNX5和SNX6在将阳离子无关的6-磷酸甘露糖受体（CI-MPR）从内体检索到跨高尔基网络（TGN）方面具有冗余功能，但其在细胞内蛋白质转运中的作用在很大程度上仍未被探索。在这里，我们报告了它与 SNX1 在介导表皮生长因子（EGF）刺激的表皮生长因子受体（EGFR）的内含体后转运中的平行功能。此外，SNX32 还与表皮生长因子受体直接相互作用，并招募 SNX5 来促进表皮生长因子受体分选到多泡体（MVB）中，以便溶酶体降解。因此，SNX32 在介导表皮生长因子受体的信号耦合内溶酶体转运方面的功能与其他 SNX-BAR 蛋白截然不同。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Traffic 生物-细胞生物学

CiteScore

8.10

自引率

2.20%

发文量

审稿时长

2 months

期刊介绍： Traffic encourages and facilitates the publication of papers in any field relating to intracellular transport in health and disease. Traffic papers span disciplines such as developmental biology, neuroscience, innate and adaptive immunity, epithelial cell biology, intracellular pathogens and host-pathogen interactions, among others using any eukaryotic model system. Areas of particular interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, the interface between signaling and trafficking or localization, protein translocation, the cell biology of adaptive an innate immunity, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement. All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision. Traffic will consider manuscripts of any length, but encourages authors to limit their papers to 16 typeset pages or less.