Biogenesis of Lysosome-related Organelles Complex-1 Subunit 1 (BLOS1) Interacts with Sorting Nexin 2 and the Endosomal Sorting Complex Required for Transport-I (ESCRT-I) Component TSG101 to Mediate the Sorting of Epidermal Growth Factor Receptor into Endo
Biogenesis of Lysosome-related Organelles Complex-1 Subunit 1 (BLOS1) Interacts with Sorting Nexin 2 and the Endosomal Sorting Complex Required for Transport-I (ESCRT-I) Component TSG101 to Mediate the Sorting of Epidermal Growth Factor Receptor into Endo
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DOI：
10.1074/jbc.m114.576561
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发表时间：
2014-09
期刊：
影响因子：
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通讯作者：
Aili Zhang;Xinchao He;Ling Zhang;Lin Yang;P. Woodman;Wei Li
中科院分区：
文献类型：
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作者：
Aili Zhang;Xinchao He;Ling Zhang;Lin Yang;P. Woodman;Wei Li
背景：EGFR 溶酶体运输过程对于 EGF 信号传导的调节非常重要。结果：BLOS1 敲低细胞中延迟的 EGFR 降解可通过与 SNX2 和 TSG101 相互作用的过表达 BLOS1 片段来恢复。结论：BLOS1 介导 EGFR 溶酶体运输。意义：增强EGFR溶酶体降解将有效治疗癌症或肺纤维化。溶酶体相关细胞器复合体 1 (BLOC-1) 的生物发生是特殊细胞器生物发生和通过内体到溶酶体运输途径对货物进行溶酶体靶向所需的分子机制的组成部分。 BLOS1 是 BLOC-1 的一个亚基，参与膜蛋白的溶酶体运输。我们发现 BLOS1 敲低细胞中表皮生长因子受体 (EGFR) 的降解和运输被延迟，但通过 BLOS1 过表达可以挽救这些细胞。 EGFR 延迟降解的一个关键特征是 BLOS1 敲低细胞或 BLOS1 敲除小鼠胚胎成纤维细胞中内溶酶体的积累。 BLOS1 与 SNX2（逆转录体亚基）和 TSG101（转运亚基-I 所需的内体分选复合物）相互作用，介导 EGFR 溶酶体运输。这些结果表明，内溶酶体运输蛋白的协调对于 EGFR 正确靶向溶酶体非常重要。
Background: EGFR lysosomal trafficking process is important for the modulation of EGF signaling. Results: Delayed EGFR degradation in BLOS1 knockdown cells is restored by the overexpressed BLOS1 fragment that interacts with both SNX2 and TSG101. Conclusion: BLOS1 mediates EGFR lysosomal trafficking. Significance: Enhancement of EGFR lysosomal degradation will be effective in the treatment of cancer or lung fibrosis. Biogenesis of lysosome-related organelles complex-1 (BLOC-1) is a component of the molecular machinery required for the biogenesis of specialized organelles and lysosomal targeting of cargoes via the endosomal to lysosomal trafficking pathway. BLOS1, one subunit of BLOC-1, is implicated in lysosomal trafficking of membrane proteins. We found that the degradation and trafficking of epidermal growth factor receptor (EGFR) were delayed in BLOS1 knockdown cells, which were rescued through BLOS1 overexpression. A key feature to the delayed EGFR degradation is the accumulation of endolysosomes in BLOS1 knockdown cells or BLOS1 knock-out mouse embryonic fibroblasts. BLOS1 interacted with SNX2 (a retromer subunit) and TSG101 (an endosomal sorting complex required for transport subunit-I) to mediate EGFR lysosomal trafficking. These results suggest that coordination of the endolysosomal trafficking proteins is important for proper targeting of EGFR to lysosomes.