Department of Biology, University of Washington, Seattle, WA 98105, U.S.A.
Biochem Soc Trans. 2022 Oct 31;50(5):1281-1291. doi: 10.1042/BST20211254.
Phagocytosis triggered by the phospholipid phosphatidylserine (PS) is key for the removal of apoptotic cells in development, tissue homeostasis and infection. Modulation of PS-mediated phagocytosis is an attractive target for therapeutic intervention in the context of atherosclerosis, neurodegenerative disease, and cancer. Whereas the mechanisms of target recognition, lipid and protein signalling, and cytoskeletal remodelling in opsonin-driven modes of phagocytosis are increasingly well understood, PS-mediated phagocytosis has remained more elusive. This is partially due to the involvement of a multitude of receptors with at least some redundancy in functioning, which complicates dissecting their contributions and results in complex downstream signalling networks. This review focusses on the receptors involved in PS-recognition, the signalling cascades that connect receptors to cytoskeletal remodelling required for phagocytosis, and recent progress in our understanding of how phagocytic cup formation is coordinated during PS-mediated phagocytosis.
磷脂酰丝氨酸(PS)引发的吞噬作用对于清除发育、组织稳态和感染过程中的凋亡细胞至关重要。在动脉粥样硬化、神经退行性疾病和癌症的背景下,调节 PS 介导的吞噬作用是治疗干预的一个有吸引力的靶点。虽然越来越多的人了解调理素驱动的吞噬作用中的靶识别、脂质和蛋白质信号以及细胞骨架重塑的机制,但 PS 介导的吞噬作用仍然更加难以捉摸。这部分是由于涉及多种受体,其功能至少存在一些冗余,这使得它们的贡献难以区分,并导致复杂的下游信号网络。这篇综述重点介绍了参与 PS 识别的受体、将受体连接到吞噬作用所需的细胞骨架重塑的信号级联,以及最近在理解 PS 介导的吞噬作用过程中如何协调吞噬杯形成方面的进展。