Controling the cytoskeleton during CEACAM3-mediated phagocytosis
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | European Journal of Cell Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0171933524000013 |
| _version_ | 1797345970608930816 |
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| author | Johannes W.P. Kuiper Helena L. Gregg Meike Schüber Jule Klein Christof R. Hauck |
| author_facet | Johannes W.P. Kuiper Helena L. Gregg Meike Schüber Jule Klein Christof R. Hauck |
| author_sort | Johannes W.P. Kuiper |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T11:26:28Z |
| format | Article |
| id | doaj.art-1813b610724f45e1a9811af94ec32820 |
| institution | Directory Open Access Journal |
| issn | 0171-9335 |
| language | English |
| last_indexed | 2024-03-08T11:26:28Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Cell Biology |
| spelling | doaj.art-1813b610724f45e1a9811af94ec328202024-01-26T05:31:39ZengElsevierEuropean Journal of Cell Biology0171-93352024-03-011031151384Controling the cytoskeleton during CEACAM3-mediated phagocytosisJohannes W.P. Kuiper0Helena L. Gregg1Meike Schüber2Jule Klein3Christof R. Hauck4Lehrstuhl Zellbiologie, Fachbereich Biologie, Universität Konstanz, GermanyLehrstuhl Zellbiologie, Fachbereich Biologie, Universität Konstanz, GermanyLehrstuhl Zellbiologie, Fachbereich Biologie, Universität Konstanz, GermanyLehrstuhl Zellbiologie, Fachbereich Biologie, Universität Konstanz, GermanyLehrstuhl Zellbiologie, Fachbereich Biologie, Universität Konstanz, Germany; Konstanz Research School Chemical Biology, Universität Konstanz, Germany; Correspondence to: Lehrstuhl Zellbiologie, Fachbereich Biologie 621, Universität Konstanz, Universitätsstrasse 10, 78457 Konstanz, Germany.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.http://www.sciencedirect.com/science/article/pii/S0171933524000013CEA-related cell adhesion moleculeImmunoreceptor tyrosine-based activation motifPhagocytosisTyrosine phosphorylationRacPathogenic bacteria |
| spellingShingle | Johannes W.P. Kuiper Helena L. Gregg Meike Schüber Jule Klein Christof R. Hauck Controling the cytoskeleton during CEACAM3-mediated phagocytosis European Journal of Cell Biology CEA-related cell adhesion molecule Immunoreceptor tyrosine-based activation motif Phagocytosis Tyrosine phosphorylation Rac Pathogenic bacteria |
| title | Controling the cytoskeleton during CEACAM3-mediated phagocytosis |
| title_full | Controling the cytoskeleton during CEACAM3-mediated phagocytosis |
| title_fullStr | Controling the cytoskeleton during CEACAM3-mediated phagocytosis |
| title_full_unstemmed | Controling the cytoskeleton during CEACAM3-mediated phagocytosis |
| title_short | Controling the cytoskeleton during CEACAM3-mediated phagocytosis |
| title_sort | controling the cytoskeleton during ceacam3 mediated phagocytosis |
| topic | CEA-related cell adhesion molecule Immunoreceptor tyrosine-based activation motif Phagocytosis Tyrosine phosphorylation Rac Pathogenic bacteria |
| url | http://www.sciencedirect.com/science/article/pii/S0171933524000013 |
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