RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment
The phagocytic integrins and complement receptors α<sub>M</sub>β<sub>2</sub>/CR3 and α<sub>X</sub>β<sub>2</sub>/CR4 are classically associated with the phagocytosis of iC3b-opsonized particles. The activation of this receptor is dependent on signals de...
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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/5/1166 |
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| author | Alvaro Torres-Gomez Jose Luis Sanchez-Trincado Víctor Toribio Raul Torres-Ruiz Sandra Rodríguez-Perales María Yáñez-Mó Pedro A. Reche Carlos Cabañas Esther M. Lafuente |
| author_facet | Alvaro Torres-Gomez Jose Luis Sanchez-Trincado Víctor Toribio Raul Torres-Ruiz Sandra Rodríguez-Perales María Yáñez-Mó Pedro A. Reche Carlos Cabañas Esther M. Lafuente |
| author_sort | Alvaro Torres-Gomez |
| collection | DOAJ |
| description | The phagocytic integrins and complement receptors α<sub>M</sub>β<sub>2</sub>/CR3 and α<sub>X</sub>β<sub>2</sub>/CR4 are classically associated with the phagocytosis of iC3b-opsonized particles. The activation of this receptor is dependent on signals derived from other receptors (inside-out signaling) with the crucial involvement of the Rap1-RIAM-Talin-1 pathway. Here, we analyze the implication of RIAM and its binding partner VASP in the signaling events occurring downstream of β<sub>2</sub> integrins (outside-in) during complement-mediated phagocytosis. To this end, we used HL-60 promyelocytic cell lines deficient in RIAM or VASP or overexpressing EGFP-tagged VASP to determine VASP dynamics at phagocytic cups. Our results indicate that RIAM-deficient HL-60 cells presented impaired particle internalization and altered integrin downstream signaling during complement-dependent phagocytosis. Similarly, VASP deficiency completely blocked phagocytosis, while VASP overexpression increased the random movement of phagocytic particles at the cell surface, with reduced internalization. Moreover, the recruitment of VASP to particle contact sites, amount of pSer157-VASP and formation of actin-rich phagocytic cups were dependent on RIAM expression. Our results suggested that RIAM worked as a relay for integrin complement receptors in outside-in signaling, coordinating integrin activation and cytoskeletal rearrangements via its interaction with VASP. |
| first_indexed | 2024-03-10T19:58:02Z |
| format | Article |
| id | doaj.art-047e95a30f824c5b924141d775342864 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:58:02Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-047e95a30f824c5b924141d7753428642023-11-19T23:47:51ZengMDPI AGCells2073-44092020-05-0195116610.3390/cells9051166RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle EngulfmentAlvaro Torres-Gomez0Jose Luis Sanchez-Trincado1Víctor Toribio2Raul Torres-Ruiz3Sandra Rodríguez-Perales4María Yáñez-Mó5Pedro A. Reche6Carlos Cabañas7Esther M. Lafuente8Department of Immunology, Ophthalmology and Otorhinolaryngology, School of Medicine, Universidad Complutense de Madrid, and Instituto (I+12), 28040 Madrid, SpainDepartment of Immunology, Ophthalmology and Otorhinolaryngology, School of Medicine, Universidad Complutense de Madrid, and Instituto (I+12), 28040 Madrid, SpainSevero Ochoa Center for Molecular Biology (CSIC-UAM), 28049 Madrid, SpainMolecular Cytogenetics and Genome Editing Unit, Human Cancer Genetics Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, SpainMolecular Cytogenetics and Genome Editing Unit, Human Cancer Genetics Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, SpainSevero Ochoa Center for Molecular Biology (CSIC-UAM), 28049 Madrid, SpainDepartment of Immunology, Ophthalmology and Otorhinolaryngology, School of Medicine, Universidad Complutense de Madrid, and Instituto (I+12), 28040 Madrid, SpainDepartment of Immunology, Ophthalmology and Otorhinolaryngology, School of Medicine, Universidad Complutense de Madrid, and Instituto (I+12), 28040 Madrid, SpainDepartment of Immunology, Ophthalmology and Otorhinolaryngology, School of Medicine, Universidad Complutense de Madrid, and Instituto (I+12), 28040 Madrid, SpainThe phagocytic integrins and complement receptors α<sub>M</sub>β<sub>2</sub>/CR3 and α<sub>X</sub>β<sub>2</sub>/CR4 are classically associated with the phagocytosis of iC3b-opsonized particles. The activation of this receptor is dependent on signals derived from other receptors (inside-out signaling) with the crucial involvement of the Rap1-RIAM-Talin-1 pathway. Here, we analyze the implication of RIAM and its binding partner VASP in the signaling events occurring downstream of β<sub>2</sub> integrins (outside-in) during complement-mediated phagocytosis. To this end, we used HL-60 promyelocytic cell lines deficient in RIAM or VASP or overexpressing EGFP-tagged VASP to determine VASP dynamics at phagocytic cups. Our results indicate that RIAM-deficient HL-60 cells presented impaired particle internalization and altered integrin downstream signaling during complement-dependent phagocytosis. Similarly, VASP deficiency completely blocked phagocytosis, while VASP overexpression increased the random movement of phagocytic particles at the cell surface, with reduced internalization. Moreover, the recruitment of VASP to particle contact sites, amount of pSer157-VASP and formation of actin-rich phagocytic cups were dependent on RIAM expression. Our results suggested that RIAM worked as a relay for integrin complement receptors in outside-in signaling, coordinating integrin activation and cytoskeletal rearrangements via its interaction with VASP.https://www.mdpi.com/2073-4409/9/5/1166phagocytosiscomplementCR3CR4Mac-1β<sub>2</sub> integrins |
| spellingShingle | Alvaro Torres-Gomez Jose Luis Sanchez-Trincado Víctor Toribio Raul Torres-Ruiz Sandra Rodríguez-Perales María Yáñez-Mó Pedro A. Reche Carlos Cabañas Esther M. Lafuente RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment Cells phagocytosis complement CR3 CR4 Mac-1 β<sub>2</sub> integrins |
| title | RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment |
| title_full | RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment |
| title_fullStr | RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment |
| title_full_unstemmed | RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment |
| title_short | RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment |
| title_sort | riam vasp module relays integrin complement receptors in outside in signaling driving particle engulfment |
| topic | phagocytosis complement CR3 CR4 Mac-1 β<sub>2</sub> integrins |
| url | https://www.mdpi.com/2073-4409/9/5/1166 |
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