程序性细胞死亡（细胞凋亡）对多细胞生物体的发育、组织和器官的动态稳定十分重要。细胞凋亡过程可分为细胞凋亡的特异性激活、执行，凋亡细胞的吞噬和降解等阶段。其中凋亡细胞的吞噬和降解过程是整个细胞凋亡程序的必要环节。凋亡细胞的清除障碍会引起诸多疾病，如哮喘、类风湿性关节炎、狼疮等炎症疾病和自身免疫紊乱等。迄今为止，关于凋亡细胞的吞噬机制研究已有许多发现，但是对于含凋亡细胞的吞噬小体的形成、成熟以及凋亡细胞的降解机制仍知之甚少。
中科院遗传与发育生物学研究所杨崇林课题组以秀丽线虫为模式研究程序性细胞死亡，通过遗传分析、基因表达、蛋白定位等实验手段，发现vps-18基因在凋亡细胞的降解过程中发挥重要作用。该研究发现vps-18在吞噬细胞中表达并发挥功能，它主要影响凋亡细胞的降解而非吞噬过程。vps-18缺失会严重地影响到与细胞内膜泡运输相关的胞内体和溶酶体的形成及成熟，从而导致胞内体和溶酶体的降解功能缺陷。该研究还发现， 在vps-18突变的线虫中，含凋亡细胞的吞噬小体不能与畸形的溶酶体融合。因此，在凋亡细胞的清除过程中，具有正常降解活性的胞内体和溶酶体与含凋亡细胞的吞噬小体之间的正常融合，对于凋亡细胞的及时清除是至关重要的。该研究因而揭示了vps-18基因参与程序性细胞死亡的作用机制，结果已在线发表于2008年10月的《细胞分子生物学》（Molecular Biology of the Cell）上。（生物谷Bioon.com）
生物谷推荐原始出处：
Molecular Biology of the Cell，doi：10.1091/mbc.E08-04-0441，Hui Xiao，Chonglin Yang
Lysosome Biogenesis Mediated by vps-18 Affects Apoptotic Cell Degradation in C. elegans
Hui Xiao,* Didi Chen,* Zhou Fang,* Jing Xu,* Xiaojuan Sun,* Song Song,* Jiajia Liu,* and Chonglin Yang*
*Key laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; Graduate School, Chinese Academy of Sciences, Beijing 100039, China
Monitoring Editor: Donald D. Newmeyer
Appropriate clearance of apoptotic cells (cell corpses) is an important step of programmed cell death. Although genetic and biochemical studies have identified several genes that regulate the engulfment of cell corpses, how these are degraded after being internalized in engulfing cell remains elusive. Here we show that VPS-18, the C. elegans homolog of yeast Vps18p, is critical to cell corpse degradation. VPS-18 is expressed and functions in engulfing cells. Deletion of vps-18 leads to significant accumulation of cell corpses that are not degraded properly. Furthermore, vps-18 mutation causes strong defects in the biogenesis of endosomes and lysosomes, thus affecting endosomal/lysosomal protein degradation. Importantly, we demonstrate that phagosomes containing internalized cell corpses are unable to fuse with lysosomes in vps-18 mutants. Our findings thus provide direct evidence for the important role of endosomal/lysosomal degradation in proper clearance of apoptotic cells during programmed cell death.
