Controling the cytoskeleton during CEACAM3-mediated phagocytosis

• Published in: European journal of cell biology Vol. 103; no. 1; p. 151384
• Main Authors: Kuiper, Johannes W.P., Gregg, Helena L., Schüber, Meike, Klein, Jule, Hauck, Christof R.
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.03.2024; Elsevier
• Subjects: actin; adhesins; CEA-related cell adhesion molecule; cell adhesion molecules; cytoskeleton; domain; family; granulocytes; guanosinetriphosphatase; humans; immunologic receptors; Immunoreceptor tyrosine-based activation motif; Pathogenic bacteria; Phagocytosis; phosphorylation; protein-tyrosine-phosphatase; Rac; species; tyrosine; Tyrosine phosphorylation; ITAM; CEA-related cell adhesion molecule; Tyrosine phosphorylation; Rac; Immunoreceptor tyrosine-based activation motif; Pathogenic bacteria; CEA; Ig; Phagocytosis; CEACAM
• ISSN: 0171-9335; 1618-1298; 1618-1298
• DOI: 10.1016/j.ejcb.2024.151384

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 (IgV)-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. •CEACAM3 is a phagocytic receptor found on granulocytes of higher primates.•CEACAM3 triggers massive, actin-driven lamellipodia formation upon engagement.•Dephosphorylation by RPTPJ and Rac-GTP scavenging by Cyri-B limit CEACAM3 action.•Interference with RPTPJ or Cyri-B can boost CEACAM3-mediated phagocytosis of human pathogens.