Wang Xiaochen, Wu Yi-Chun, Fadok Valerie A, Lee Ming-Chia, Gengyo-Ando Keiko, Cheng Li-Chun, Ledwich Duncan, Hsu Pei-Ken, Chen Jia-Yun, Chou Bin-Kuan, Henson Peter, Mitani Shohei, Xue Ding
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Science. 2003 Nov 28;302(5650):1563-6. doi: 10.1126/science.1087641.
During apoptosis, phosphatidylserine, which is normally restricted to the inner leaflet of the plasma membrane, is exposed on the surface of apoptotic cells and has been suggested to act as an "eat-me" signal to trigger phagocytosis. It is unclear how phagocytes recognize phosphatidylserine. Recently, a putative phosphatidylserine receptor (PSR) was identified and proposed to mediate recognition of phosphatidylserine and phagocytosis. We report that psr-1, the Caenorhabditis elegans homolog of PSR, is important for cell corpse engulfment. In vitro PSR-1 binds preferentially phosphatidylserine or cells with exposed phosphatidylserine. In C. elegans, PSR-1 acts in the same cell corpse engulfment pathway mediated by intracellular signaling molecules CED-2 (homologous to the human CrkII protein), CED-5 (DOCK180), CED-10 (Rac GTPase), and CED-12 (ELMO), possibly through direct interaction with CED-5 and CED-12. Our findings suggest that PSR-1 is likely an upstream receptor for the signaling pathway containing CED-2, CED-5, CED-10, and CED-12 proteins and plays an important role in recognizing phosphatidylserine during phagocytosis.
在细胞凋亡过程中，通常局限于质膜内小叶的磷脂酰丝氨酸会暴露在凋亡细胞表面，并被认为作为一种“吃我”信号触发吞噬作用。目前尚不清楚吞噬细胞如何识别磷脂酰丝氨酸。最近，一种假定的磷脂酰丝氨酸受体（PSR）被鉴定出来，并被认为介导磷脂酰丝氨酸的识别和吞噬作用。我们报道，PSR在秀丽隐杆线虫中的同源物psr-1对细胞尸体吞噬很重要。在体外，PSR-1优先结合磷脂酰丝氨酸或磷脂酰丝氨酸暴露的细胞。在秀丽隐杆线虫中，PSR-1作用于由细胞内信号分子CED-2（与人CrkII蛋白同源）、CED-5（DOCK180）、CED-10（Rac GTP酶）和CED-12（ELMO）介导的同一细胞尸体吞噬途径，可能是通过与CED-5和CED-12直接相互作用。我们的研究结果表明，PSR-1可能是包含CED-2、CED-5、CED-10和CED-12蛋白的信号通路的上游受体，在吞噬过程中识别磷脂酰丝氨酸方面发挥重要作用。
