2012年4月2日，北京生命科學(xué)研究所王曉晨實驗室和中科院生物物理所歐光朔實驗室合作在The Journal of Cell Biology雜志發(fā)表題為“Autophagy genes function sequentially to promote apoptotic cell corpse degradation in the engulfing cell,，”的文章,，文章中，研究者揭示了細胞自噬基因在凋亡細胞降解過程中的新功能,。
高等動物中凋亡細胞清除缺陷可導(dǎo)致炎癥,、免疫紊亂和神經(jīng)退行性疾病。因此,，研究凋亡細胞清除過程具有重要的意義,。細胞自噬與凋亡細胞清除是兩個均高度依賴于溶酶體降解功能的生物學(xué)過程,。吞噬細胞中細胞自噬缺陷是否會影響凋亡細胞清除？為了研究這個問題,，作者利用轉(zhuǎn)盤碟片共聚焦顯微鏡記錄方法,，在單細胞和亞細胞水平上，實時跟蹤了野生型和兩個細胞自噬突變體atg-18和epg-5幼齡一期秀麗線蟲hyp7表皮細胞吞噬并降解Q凋亡細胞的完整過程,。研究表明,，與野生型相比，突變體中Q凋亡細胞被表皮細胞吞噬所用時間無顯著差異,，而降解過程顯著延遲,。表皮細胞特異性表達的ATG-18和EPG-5可挽救突變體缺陷，表明atg-18和epg-5作用于吞噬細胞內(nèi)促進Q凋亡細胞降解過程,。與野生型相比,，突變體中吞噬體表面募集凋亡細胞降解所必需的RAB-5、RAB-7蛋白以及吞噬體-溶酶體融合顯著延遲,。通過實時跟蹤表皮細胞內(nèi)表達的細胞自噬蛋白EGP-5,，ATG-18和LGG-1與熒光分子的融合蛋白，作者發(fā)現(xiàn)它們分別在不同的階段被招募到吞噬體表面或附近,，暗示它們可能作用于凋亡細胞降解的不同步驟,。
李薇博士（生物物理所）、鄒煒博士（NIBS）,、楊藝紅博士（生物物理所）和柴詠平博士（生物物理所）為本文的共同第一作者,， 其他作者包括陳寶惠博士（NIBS）、程世亞（NIBS）和田東（生物物理所）,。王曉晨博士（NIBS）,、Ron Vale博士（UCSF）和歐光朔博士（生物物理所）為本文的共同通訊作者。在北京生命科學(xué)研究所的研究工作受到科技部和北京市政府的支持,。（生物谷Bioon.com）
doi:10.1083/jcb.201111053
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Autophagy genes function sequentially to promote apoptotic cell corpse degradation in the engulfing cell
Wei Li1, Wei Zou2, Yihong Yang1, Yongping Chai1, Baohui Chen2, Shiya Cheng2, Dong Tian1, Xiaochen Wang2, Ronald D. Vale3,4, and Guangshuo Ou1,3,4
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.
