Phagocytosis, an innate defense mechanism of multicellular animals, is initiated by specialized surface receptors. A phagocytic receptor expressed by human polymorphonuclear granulocytes, the major professional phagocytes in our body, is one of the fastest evolving human proteins implying a special role in human biology. This receptor, CEACAM3, is a member of the CarcinoEmbryonic Antigen-related Cell Adhesion Molecule (CEACAM) family and dedicated to the immediate recognition and rapid internalization of human-restricted pathogens. In this focused contribution, we will review the special adaptations of this protein, which co-evolves with different species of mucosa-colonizing bacteria. While the extracellular Immunoglobulin-variable (Ig)-like domain recognizes various bacterial adhesins, an Immunoreceptor Tyrosine-based Activation Motif (ITAM)-like sequence in the cytoplasmic tail of CEACAM3 constitutes the central signaling hub to trigger actin rearrangements needed for efficient phagocytosis. A major emphasis of this review will be placed on recent findings, which have revealed the multi-level control of this powerful phagocytic device. As tyrosine phosphorylation and small GTPase activity are central for CEACAM3-mediated phagocytosis, the counterregulation of CEACAM3 activity involves the receptor-type protein tyrosine phosphatase J (PTPRJ) as well as the Rac-GTP scavenging protein Cyri-B. Interference with such negative regulatory circuits has revealed that CEACAM3-mediated phagocytosis can be strongly enhanced. In principle, the knowledge gained by studying CEACAM3 can be applied to other phagocytic systems and opens the door to treatments, which boost the phagocytic capacity of professional phagocytes.

中文翻译：

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在 CEACAM3 介导的吞噬作用过程中控制细胞骨架

吞噬作用是多细胞动物的一种先天防御机制，由专门的表面受体启动。由人类多形核粒细胞（我们体内主要的专业吞噬细胞）表达的吞噬细胞受体是进化最快的人类蛋白质之一，意味着在人类生物学中具有特殊作用。这种受体 CEACAM3 是癌胚抗原相关细胞粘附分子 (CEACAM) 家族的成员，致力于立即识别和快速内化人类限制的病原体。在这篇重点贡献中，我们将回顾这种蛋白质的特殊适应，它与不同种类的粘膜定植细菌共同进化。虽然细胞外免疫球蛋白可变 (Ig) 样结构域可识别各种细菌粘附素，但 CEACAM3 胞质尾部中基于免疫受体酪氨酸的激活基序 (ITAM) 样序列构成了中央信号传导中枢，可触发有效吞噬所需的肌动蛋白重排。本次综述的重点将放在最近的发现上，这些发现揭示了这种强大的吞噬装置的多级控制。由于酪氨酸磷酸化和小 GTP 酶活性是 CEACAM3 介导的吞噬作用的核心，因此 CEACAM3 活性的反调节涉及受体型蛋白酪氨酸磷酸酶 J (PTPRJ) 以及 Rac-GTP 清除蛋白 Cyri-B。干扰此类负调节回路表明，CEACAM3 介导的吞噬作用可以得到强烈增强。原则上，通过研究 CEACAM3 获得的知识可以应用于其他吞噬系统，并为治疗打开大门，从而增强专业吞噬细胞的吞噬能力。