Rab14通过促进V-ATPase溶酶递送来抑制病原体,从而驱动溶酶酸性酸化
Zehui Lei1,2, Lihua Qiang3, Pupu Ge1
1Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Nature communications
|March 2, 2026
概括
研究人员发现Rab14,一个宿主蛋白质,通过增强病原体清除的溶酶体酸化作用,作为对细菌和病毒的广泛限制因子,提供了新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 微生物学 微生物学
背景情况:
- 宿主限制因素对于对病原体的内在免疫力至关重要.
- 虽然病毒限制因子得到了充分的研究,但具有广谱活性的细菌对应物尚未得到充分的研究.
- 溶酶体酸化是病原体清除的关键细胞过程.
研究的目的:
- 为了确定具有广谱抗微生物活性的新型宿主限制因素.
- 阐明这些因素限制病原体生长的机制.
- 探索针对传染病的宿主导疗法 (HDT) 的潜在目标.
主要方法:
- 对促进溶酶体酸化的宿主因子进行查.
- 通过功能查来识别Rab14.
- 研究Rab14与CAMK2D和V-ATPase组件的分子相互作用.
- 评估Rab14对细胞模型中的病原体清除的影响.
主要成果:
- Rab14被确定为一种对细菌和病毒具有广泛活性的宿主限制因子.
- 拉布14通过调节V-ATPase贩运来增强 lysosomal 酸化.
- 在机理上,Rab14与CAMK2D结合,抑制V0a1酸化并促进V-ATPase向 lysosomes的递送.
- 这种Rab14-CAMK2D-V-ATPase轴促进病原体的清除.
结论:
- 拉布14代表了一种针对各种病原体的新型内在免疫机制.
- Rab14-CAMK2D-V-ATPase通路是传染病的潜在治疗标.
- 这一发现扩大了对对抗耐药病原体的宿主导疗法的理解.
相关概念视频
Receptor-mediated Endocytosis
Overview
Receptor-mediated Endocytosis
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
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After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...


