RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment

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Torres Gómez, Álvaro and Sánchez Trincado López, José Luis and Toribio, Víctor and Torres-Ruiz, Raul and Rodríguez-Perales, Sandra and Yáñez-Mó, María and Reche, Pedro A and Cabañas Gutiérrez, Carlos and Lafuente Duarte, María Esther (2020) RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment. Cells, 9 (5). p. 1166. ISSN 2073-4409

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Official URL: https://doi.org/10.3390/cells9051166




Abstract

The phagocytic integrins and complement receptors αMβ2/CR3 and αXβ2/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 β2 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.


Item Type:Article
Uncontrolled Keywords:phagocytosis; complement; CR3; CR4; Mac-1; β2 integrins; RIAM; VASP; outside-in
Subjects:Medical sciences > Medicine > Ophtalmology
ID Code:65747
Deposited On:26 May 2021 16:04
Last Modified:27 May 2021 08:06

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