3月26日,，中科院生物物理研究所歐光朔研究組在《細(xì)胞生物學(xué)雜志》（Journal of Cell Biology）上在線發(fā)表題為Autophagy genes function sequentially to promote apoptotic cell corpse degradation in the engulfing cell的論文,，報(bào)道了自體吞噬基因在吞噬細(xì)胞中發(fā)揮作用，促進(jìn)凋亡細(xì)胞的降解,。
凋亡細(xì)胞的清除是細(xì)胞死亡的最終環(huán)節(jié),，其異常會(huì)導(dǎo)致炎癥和自身免疫紊亂。細(xì)胞自體吞噬作用是指胞內(nèi)囊泡包裹胞質(zhì)中的內(nèi)含物運(yùn)送到溶酶體中進(jìn)行清除的過程,。前人研究表明,，自體吞噬基因在細(xì)胞凋亡過程中發(fā)揮功能，促進(jìn)凋亡細(xì)胞產(chǎn)生被吞噬細(xì)胞識(shí)別所需的信號(hào),。
這項(xiàng)新的研究以線蟲Q神經(jīng)前體細(xì)胞發(fā)育產(chǎn)生的凋亡細(xì)胞為模型,，發(fā)現(xiàn)自體吞噬基因atg-18和epg-5并不在凋亡細(xì)胞中起作用，而是在吞噬細(xì)胞中發(fā)揮功能,；自體吞噬蛋白在吞噬細(xì)胞中被招募到凋亡細(xì)胞表面,，調(diào)控內(nèi)涵體和溶酶體與凋亡Q細(xì)胞的融合，促進(jìn)凋亡Q細(xì)胞的降解,。該發(fā)現(xiàn)拓展了人們在自體吞噬基因調(diào)控細(xì)胞凋亡方面的認(rèn)識(shí),。
為了研究自體吞噬蛋白和其他蛋白被招募到凋亡細(xì)胞上的時(shí)序關(guān)系，歐光朔研究組改造了一種藍(lán)色熒光蛋白（TagBFP）,，使之適用與線蟲,，與GFP和mCherry共同使用，實(shí)現(xiàn)了在線蟲中的三色熒光活體時(shí)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.
