Abstract：
Pattern recognition receptors (PRRs) mediate the innate immune responses and play a crucial role in host defense against pathogen infections. Apextrin C-terminal (ApeC)-containing proteins (ACPs), a newly discovered class of PRRs specific to invertebrates, recognize pathogens through their ApeC domain as intracellular or extracellular effectors. However, the other immunological functions of ACPs remain unclear. In this study, a membrane-localized ACP receptor was identified in the sea cucumber Apostichopus japonicus (denoted as AjACP1). The ApeC domain of AjACP1, which was located outside of its cell membrane, exhibited the capability to recognize and aggregate Vibrio splendidus. AjACP1 was upregulated upon V. splendidus infection, internalizing into the cytoplasm of coelomocytes. AjACP1 overexpression enhanced the phagocytic activity of coelomocytes against V. splendidus, while knockdown of AjACP1 by RNA interfere inhibited coelomocyte endocytosis. Inhibitor experiments indicated that AjACP1 regulated coelomocyte phagocytosis through the actin-dependent endocytic signaling pathway. Further investigation revealed that AjACP1 interacted with the subunit of the actin-related protein 2/3 complex ARPC2, promoting F-actin polymerization and cytoskeletal rearrangement and thereby affecting the coelomocyte phagocytosis of V. splendidus via the actin-dependent endocytic signaling pathway. As a novel membrane PRR, AjACP1 mediates the recognition and phagocytic activity of coelomocytes against V. splendidus through the AjACP1-ARPC2-F-actin polymerization and cytoskeletal rearrangement pathway.
摘要：
模式识别受体（PRR）介导先天性免疫反应，并在宿主防御病原体感染中起关键作用。含ApextrinC末端（ApeC）的蛋白质（ACP），一种新发现的无脊椎动物特有的PRRs，通过其ApeC结构域识别病原体作为细胞内或细胞外效应子。然而,ACPs的其他免疫功能尚不清楚。在这项研究中,在海参刺参中鉴定出膜定位的ACP受体（表示为AjACP1）。AjACP1的ApeC域位于其细胞膜外,表现出识别和聚集脾弧菌的能力。AjACP1在脾弧菌感染时上调，内化到腔体细胞的细胞质中。AjACP1过表达增强了腔体细胞对脾弧菌的吞噬活性，而RNA干扰AjACP1的敲除抑制了腔体细胞的内吞作用。抑制剂实验表明，AjACP1通过肌动蛋白依赖性胞吞信号通路调节体腔细胞的吞噬作用。进一步的研究表明，AjACP1与肌动蛋白相关蛋白2/3复合物ARPC2的亚基相互作用，促进F-肌动蛋白聚合和细胞骨架重排，从而通过肌动蛋白依赖性内吞信号通路影响脾弧菌的腹腔细胞吞噬作用。作为一种新型的膜PRR，AjACP1通过AjACP1-ARPC2-F-肌动蛋白聚合和细胞骨架重排途径介导腔体细胞对脾弧菌的识别和吞噬活性。
