RT Journal Article
T1 RIAM (Rap1-interacting adaptor molecule) regulates complement-dependent phagocytosis
A1 Medraño Fernandez, Iria
A1 Reyes Manzanas, Raquel
A1 Olazabal, Isabel
A1 Rodríguez, Elena
A1 Sánchez Madrid, Francisco
A1 Boussiotis, Vassiliki A.
A1 Reche Gallardo, Pedro Antonio
A1 Cabañas Gutiérrez, Carlos
A1 Lafuente Duarte, María Esther
AB Phagocytosis mediated by the complement receptor CR3 (also known as integrin αMß2 or Mac-1) is regulated by the recruitment of talin to the cytoplasmic tail of the ß2 integrin subunit. Talin recruitment to this integrin is dependent on Rap1 activation. However, the mechanism by which Rap1 regulates this event and CR3-dependent phagocytosis remains largely unknown. In the present work, we examined the role of the Rap1 effector RIAM, a talin-binding protein, in the regulation of complement-mediated phagocytosis. Using the human myeloid cell lines HL-60 and THP-1, we determined that knockdown of RIAM impaired αMß2 integrin affinity changes induced by stimuli fMLP and LPS. Phagocytosis of complement-opsonized RBC particles, but not of IgG-opsonized RBC particles, was impaired in RIAM knockdown cells. Rap1 activation via EPAC induced by 8-pCPT-2'-O-Me-cAMP resulted in an increase of complement-mediated phagocytosis that was abrogated by knockdown of RIAM in HL-60 and THP-1 cell lines and in macrophages derived from primary monocytes. Furthermore, recruitment of talin to ß2 integrin during complement-mediated phagocytosis was reduced in RIAM knockdown cells. These results indicate that RIAM is a critical component of the phagocytosis machinery downstream of Rap1 and mediates its function by recruiting talin to the phagocytic complement receptors.
PB Springer
SN 1420-682X
SN 1420-9071
YR 2013
FD 2013-02-19
LK https://hdl.handle.net/20.500.14352/116153
UL https://hdl.handle.net/20.500.14352/116153
LA eng
NO Medraño-Fernandez, I., Reyes, R., Olazabal, I., Rodriguez, E., Sanchez-Madrid, F., Boussiotis, V. A., Reche, P. A., Cabañas, C., & Lafuente, E. M. (2013). RIAM (Rap1-interacting adaptor molecule) regulates complement-dependent phagocytosis. Cellular and molecular life sciences : CMLS, 70(13), 2395–2410. https://doi.org/10.1007/s00018-013-1268-6
NO Ministerio Español de Ciencia e Innovación (España)
NO Comunidad Autónoma de Madrid
NO Universidad Complutense de Madrid
NO National Institutes of Health (USA)
DS Docta Complutense
RD 6 abr 2025