2024-03-28T17:57:43Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/2125252021-12-28T16:05:12Zcom_10261_79com_10261_1col_10261_332
00925njm 22002777a 4500
dc
Torres-Gomez, Alvaro
author
Sanchez-Trincado, Jose Luis
author
Toribio, Víctor
author
Torres-Ruiz, Raul
author
Rodríguez-Perales, Sandra
author
Yáñez-Mó, María
author
Reche, Pedro A.
author
Cabañas, Carlos
author
Lafuente, Esther M.
author
2020
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.
Cells 9(5): 1166 (2020)
http://hdl.handle.net/10261/212525
10.3390/cells9051166
2073-4409
http://dx.doi.org/10.13039/501100011033
http://dx.doi.org/10.13039/501100002911
http://dx.doi.org/10.13039/501100003329
32397169
Phagocytosis
Complement
CR3
CR4
Mac-1
β2 integrins
RIAM
VASP
Outside-in
RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment