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Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell+Mol+Life+Sci 2013 ; 70 (13): 2395-410 Nephropedia Template TP
Cell Mol Life Sci 2013[Jul]; 70 (13): 2395-410 PMID23420480show ga
Phagocytosis mediated by the complement receptor CR3 (also known as integrin ?M?2 or Mac-1) is regulated by the recruitment of talin to the cytoplasmic tail of the ?2 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 promyelocytic cell lines HL-60 and THP-1, we determined that knockdown of RIAM impaired ?M?2 integrin affinity changes induced by fMLP. Phagocytosis of complement-opsonized RBC particles, but not 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 the phagocytic cup 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 phagocytic complement receptors.