3月26日,中科院生物物理研究所欧光朔研究组在《细胞生物学杂志》(Journal of Cell Biology)上在线发表题为Autophagy genes function sequentially to promote apoptotic cell corpse degradation in the engulfing cell的论文,报道了自体吞噬基因在吞噬细胞中发挥作用,促进凋亡细胞的降解。
凋亡细胞的清除是细胞死亡的最终环节,其异常会导致炎症和自身免疫紊乱。细胞自体吞噬作用是指胞内囊泡包裹胞质中的内含物运送到溶酶体中进行清除的过程。前人研究表明,自体吞噬基因在细胞凋亡过程中发挥功能,促进凋亡细胞产生被吞噬细胞识别所需的信号。
这项新的研究以线虫Q神经前体细胞发育产生的凋亡细胞为模型,发现自体吞噬基因atg-18和epg-5并不在凋亡细胞中起作用,而是在吞噬细胞中发挥功能;自体吞噬蛋白在吞噬细胞中被招募到凋亡细胞表面,调控内涵体和溶酶体与凋亡Q细胞的融合,促进凋亡Q细胞的降解。该发现拓展了人们在自体吞噬基因调控细胞凋亡方面的认识。
为了研究自体吞噬蛋白和其他蛋白被招募到凋亡细胞上的时序关系,欧光朔研究组改造了一种蓝色荧光蛋白(TagBFP),使之适用与线虫,与GFP和mCherry共同使用,实现了在线虫中的三色荧光活体时序成像。(生物谷 bioon.com)
doi:doi: 10.1083/jcb.201111053
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Autophagy genes function sequentially to promote apoptotic cell corpse degradation in the engulfing cell
Wei Li, Wei Zou, Yihong Yang, Yongping Chai, Baohui Chen, Shiya Cheng, Dong Tian, Xiaochen Wang, Ronald D. Vale,Guangshuo Ou
Apoptotic cell degradation is a fundamental process for organism development, and impaired clearance causes inflammatory or autoimmune disease. Although autophagy genes were reported to be essential for exposing the engulfment signal on apoptotic cells, their roles in phagocytes for apoptotic cell removal are not well understood. In this paper, we develop live-cell imaging techniques to study apoptotic cell clearance in the Caenorhabditis elegans Q neuroblast lineage. We show that the autophagy proteins LGG-1/LC3, ATG-18, and EPG-5 were sequentially recruited to internalized apoptotic Q cells in the phagocyte. In atg-18 or epg-5 mutants, apoptotic Q cells were internalized but not properly degraded; this phenotype was fully rescued by the expression of autophagy genes in the phagocyte. Time-lapse analysis of autophagy mutants revealed that recruitment of the small guanosine triphosphatases RAB-5 and RAB-7 to the phagosome and the formation of phagolysosome were all significantly delayed. Thus, autophagy genes act within the phagocyte to promote apoptotic cell degradation.