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| Home > Articles > Published articles > RIAM-VASP Module Relays Integrin Complement Receptors in Outside-In Signaling Driving Particle Engulfment |
(Universidad Complutense de Madrid. Departamento de Inmunología, Oftalmología y Otorrinolaringología) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Centro Nacional de Investigaciones Oncológicas) (Universidad Autónoma de Madrid, Departamento de Biología Molecular) (Centro de Biología Molecular Severo Ochoa) (Universidad Complutense de Madrid. Departamento de Inmunología, Oftalmología y Otorrinolaringología)| Date: | 2020 |
| 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. |
| Grants: | Ministerio de Economía y Competitividad SAF2016-77096-R Ministerio de Economía y Competitividad BIO2014:54164-R Ministerio de Economía y Competitividad BIO2017-86500-R Ministerio de Economía y Competitividad BIO2017-91272-EXP Ministerio de Economía y Competitividad PI17-02303 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | CR3 ; CR4 ; Mac-1 ; RIAM ; VASP ; Complement ; Outside-in ; Phagocytosis ; β2 integrins |
| Published in: | Cells, Vol. 9 Núm. 5 (august 2020) , ISSN 2073-4409 |
