RIAM (Rap1-interacting adaptor molecule) regulates complement-dependent phagocytosis

Cell Mol Life Sci. 2013 Jul;70(13):2395-410. doi: 10.1007/s00018-013-1268-6. Epub 2013 Feb 19.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adaptor Proteins, Signal Transducing / physiology*
  • CD18 Antigens / metabolism
  • CD18 Antigens / physiology
  • Cells, Cultured
  • Complement System Proteins / physiology
  • Gene Knockdown Techniques
  • HL-60 Cells
  • Humans
  • Macrophage-1 Antigen / physiology
  • Macrophages / cytology
  • Macrophages / metabolism
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Models, Biological
  • Neutrophils / cytology
  • Neutrophils / metabolism
  • Phagocytosis / physiology*
  • Talin / metabolism
  • Talin / physiology
  • rap1 GTP-Binding Proteins / metabolism
  • rap1 GTP-Binding Proteins / physiology


  • APBB1IP protein, human
  • Adaptor Proteins, Signal Transducing
  • CD18 Antigens
  • Macrophage-1 Antigen
  • Membrane Proteins
  • Talin
  • Complement System Proteins
  • rap1 GTP-Binding Proteins