Two distinct cytoplasmic regions of the beta2 integrin chain regulate RhoA function during phagocytosis

Agnès Wiedemann, Jayesh C Patel, Jenson Lim, Andy Tsun, Yvette van Kooyk, Emmanuelle Caron

Research output: Contribution to journalArticleAcademicpeer-review

51 Citations (Scopus)


AlphaMbeta2 integrins mediate phagocytosis of opsonized particles in a process controlled by RhoA, Rho kinase, myosin II, Arp2/3, and actin polymerization. AlphaMbeta2, Rho, Arp2/3, and F-actin accumulate underneath bound particles; however, the mechanism regulating Rho function during alphaMbeta2-mediated phagocytosis is poorly understood. We report that the binding of C3bi-opsonized sheep red blood cells (RBCs) to alphaMbeta2 increases Rho-GTP, but not Rac-GTP, levels. Deletion of the cytoplasmic domain of beta2, but not of alphaM, abolished Rho recruitment and activation, as well as phagocytic uptake. Interestingly, a 16-amino acid (aa) region in the membrane-proximal half of the beta2 cytoplasmic domain was necessary for activating Rho. Three COOH-terminal residues (aa 758-760) were essential for beta2-induced accumulation of Rho at complement receptor 3 (CR3) phagosomes. Activation of Rho was necessary, but not sufficient, for its stable recruitment underneath bound particles or for uptake. However, recruitment of active Rho was sufficient for phagocytosis. Our data shed light on the mechanism of outside-in signaling, from ligated integrins to the activation of Rho GTPase signaling.

Original languageEnglish
Pages (from-to)1069-79
Number of pages11
JournalJournal of cell biology
Issue number7
Publication statusPublished - 27 Mar 2006


  • Actins/metabolism
  • Amino Acid Sequence
  • Animals
  • CD18 Antigens/genetics
  • COS Cells
  • Cell Line, Tumor
  • Cercopithecus aethiops
  • Complement C3b/chemistry
  • Erythrocytes/chemistry
  • Guanosine Triphosphate/metabolism
  • Macrophage-1 Antigen/genetics
  • Macrophages/drug effects
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Phagocytosis/drug effects
  • Phagosomes/metabolism
  • Tetradecanoylphorbol Acetate/pharmacology
  • Threonine/genetics
  • Transfection
  • rac1 GTP-Binding Protein/metabolism
  • rhoA GTP-Binding Protein/genetics

Cite this