State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
School of Life Sciences, Yunnan University, Kunming, China.
Traffic. 2024 Jul;25(7):e12952. doi: 10.1111/tra.12952.
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.
SNX32 是进化上保守的 Phox（PX）同源结构域和 Bin/Amphiphysin/Rvs（BAR）结构域富含分选连接蛋白（SNX-BAR）家族蛋白的成员，该家族蛋白在分拣和内体货物的膜运输中发挥重要作用。尽管 SNX32 与 SNX6 具有最高的氨基酸序列同源性，并且被认为与 SNX5 和 SNX6 在从内体到反式高尔基网络（TGN）中阳离子非依赖性甘露糖-6-磷酸受体（CI-MPR）的回收中具有冗余功能，但它在细胞内蛋白质运输中的作用仍在很大程度上尚未得到探索。在这里，我们报告它与 SNX1 平行发挥作用，介导表皮生长因子（EGF）刺激的表皮生长因子受体（EGFR）的餐后内体运输。此外，SNX32 与 EGFR 直接相互作用，并招募 SNX5 促进 EGF-EGFR 分拣到多泡体（MVB）中进行溶酶体降解。因此，SNX32 与其他 SNX-BAR 蛋白的功能不同，可介导信号偶联的 EGFR 内体溶酶体运输。
