传出细胞增多
细胞生物学
整合素
吞噬作用
纤维连接蛋白
受体
细胞凋亡
信号转导
生物
化学
巨噬细胞
生物化学
细胞外基质
体外
作者
Juyeon Lee,Boyeon Park,Byeongjin Moon,Jeong‐Jun Park,Hyunji Moon,Kwanhyeong Kim,Sang-Ah Lee,Deokhwan Kim,Chanhyuk Min,Dae-Hee Lee,Gwangrog Lee,Daeho Park
标识
DOI:10.1038/s41418-018-0238-9
摘要
An essential step during clearance of apoptotic cells is the recognition of phosphatidylserine (PS) exposed on apoptotic cells by its receptors on phagocytes. Tim-4 directly binding to PS and functioning as a tethering receptor for phagocytosis of apoptotic cells has been extensively studied over the past decade. However, the molecular mechanisms by which Tim-4 collaborates with other engulfment receptors during efferocytosis remain elusive. By comparing efferocytosis induced by Tim-4 with that by Anxa5-GPI, an artificial tethering receptor, we found that Tim-4 possesses auxiliary machinery to induce a higher level of efferocytosis than Anxa5-GPI. To search for that, we performed a yeast two-hybrid screen and identified Fibronectin (Fn1) as a novel Tim-4-associating protein. Tim-4 directly associated with Fn1 and formed a complex with integrins via the association of Fn1. Through Tim-4-/- mice and cell-based assays, we found that modulation of the Fn1 level affected efferocytosis induced by Tim-4 and disruption of the interaction between Tim-4 and Fn1 abrogated Tim-4-mediated efferocytosis. In addition, Tim-4 depletion attenuated integrin signaling activation and perturbation of integrin signaling suppressed Tim-4-promoted efferocytosis. Taken together, the data suggest that Fn1 locates Tim-4 and integrins in close proximity by acting as a scaffold, resulting in synergistic cooperation of Tim-4 with integrins for efficient efferocytosis.
科研通智能强力驱动
Strongly Powered by AbleSci AI