程序性細胞死亡（細胞凋亡）對多細胞生物體的發(fā)育、組織和器官的動態(tài)穩(wěn)定十分重要,。細胞凋亡過程可分為細胞凋亡的特異性激活、執(zhí)行,，凋亡細胞的吞噬和降解等階段,。其中凋亡細胞的吞噬和降解過程是整個細胞凋亡程序的必要環(huán)節(jié)。凋亡細胞的清除障礙會引起諸多疾病,，如哮喘,、類風(fēng)濕性關(guān)節(jié)炎、狼瘡等炎癥疾病和自身免疫紊亂等,。迄今為止,，關(guān)于凋亡細胞的吞噬機制研究已有許多發(fā)現(xiàn)，但是對于含凋亡細胞的吞噬小體的形成,、成熟以及凋亡細胞的降解機制仍知之甚少,。
中科院遺傳與發(fā)育生物學(xué)研究所楊崇林課題組以秀麗線蟲為模式研究程序性細胞死亡，通過遺傳分析,、基因表達,、蛋白定位等實驗手段，發(fā)現(xiàn)vps-18基因在凋亡細胞的降解過程中發(fā)揮重要作用,。該研究發(fā)現(xiàn)vps-18在吞噬細胞中表達并發(fā)揮功能,，它主要影響凋亡細胞的降解而非吞噬過程。vps-18缺失會嚴重地影響到與細胞內(nèi)膜泡運輸相關(guān)的胞內(nèi)體和溶酶體的形成及成熟,，從而導(dǎo)致胞內(nèi)體和溶酶體的降解功能缺陷,。該研究還發(fā)現(xiàn),， 在vps-18突變的線蟲中,，含凋亡細胞的吞噬小體不能與畸形的溶酶體融合。因此,，在凋亡細胞的清除過程中,，具有正常降解活性的胞內(nèi)體和溶酶體與含凋亡細胞的吞噬小體之間的正常融合,，對于凋亡細胞的及時清除是至關(guān)重要的。該研究因而揭示了vps-18基因參與程序性細胞死亡的作用機制,，結(jié)果已在線發(fā)表于2008年10月的《細胞分子生物學(xué)》（Molecular Biology of the Cell）上,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
