Annexin I is an endogenous ligand that mediates apoptotic cell engulfment
Annexin I is an endogenous ligand that mediates apoptotic cell engulfment
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DOI：
10.1016/s1534-5807(03)00090-x
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发表时间：
2003-04-01
影响因子：
11.8
通讯作者：
Han, DK
中科院分区：
文献类型：
--
作者：
Arur, S;Uche, UE;Han, DK
凋亡细胞的吞噬需要垂死细胞呈递新的细胞表面配体。使用差异蛋白质组学技术，我们发现膜联蛋白I是一种半胱天酶依赖的吞噬配体；它从细胞质溶胶中招募并输出到外质膜小叶，与磷脂酰丝氨酸共定位，是有效清除凋亡细胞所必需的。此外，磷脂酰丝氨酸受体（PSR）在凋亡细胞周围聚集表明需要膜联蛋白1。在线虫线虫中，膜联蛋白同源物的下调会阻止咽部细胞尸体的有效吞噬。这些结果为凋亡细胞如何被清除提供了新的机制见解，并可能解释慢性炎症性疾病的致病机制，其中膜联蛋白I自身抗体已被描述。
Engulfment of apoptotic cells requires presentation of new cell surface ligands by the dying cells. Using a differential proteomics technology, we identify that annexin I is a caspase-dependent engulfment ligand; it is recruited from the cytosol and exported to the outer plasma membrane leaflet, colocalizes with phosphatidylserine, and is required for efficient clearance of apoptotic cells. Furthermore, phosphatidylserine receptor (PSR) clustering around apoptotic cells indicates a requirement for annexin I. In the nematode Caenorhabditis elegans, downregulation of the annexin homolog prevents efficient engulfment of pharyngeal cell corpses. These results provide novel mechanistic insights into how apoptotic cells are removed and may explain a pathogenic mechanism of chronic inflammatory diseases where annexin I autoantibodies have been described.