溶解体酶贩运因子LYSET使细胞外蛋白的营养利用成为可能
Catarina Pechincha1,2, Sven Groessl1,2, Robert Kalis3,4
1Cell Signaling and Metabolism, German Cancer Research Center (DKFZ), Heidelberg, Germany.
概括
哺乳动物细胞利用细胞外蛋白制造氨基酸,这是癌症生长的关键过程. 研究人员发现LYSET (TMEM251) 对于溶解体酶转移和营养吸收至关重要,这揭示了它在癌症代谢和溶解体储存障碍中的作用.
科学领域:
- 细胞生物学
- 分子生物学
- 生物化学
背景情况:
- 哺乳动物细胞可以通过巨细胞和细胞外蛋白的溶解体降解合成氨基酸.
- 癌细胞利用这种途径在营养有限的瘤微环境中生长.
研究的目的:
- 识别用于利用细胞外蛋白质作为氨基酸来源的关键蛋白质.
- 阐明LYSET (TMEM251) 在细胞营养获取和 lysosomal 功能中的分子机制.
主要方法:
- 在定义的营养条件下进行基因选,以确定必要的基因.
- 在戈尔吉仪器中进行了蛋白质关联研究.
- 在LYSET缺乏的细胞中评估了 lysosomal酶活性和货物周转率.
主要成果:
- 鉴定出LYSET (TMEM251) 是一种选择性地消耗细胞外蛋白质的跨膜蛋白.
- 在Golgi中与GlcNAc-1-转化酶结合,使其稳定.
- LYSET 缺乏导致 lysosomal 酶的消耗和宏细胞和自细胞的循环受损.
结论:
- LYSET是溶解体酶运输途径的关键组成部分.
- LYSET功能障碍有助于遗传性溶酶体储存障碍的发生.
- LYSET可能是抑制癌细胞代谢适应的治疗点.
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