Coupling of β2 integrins to actin by a mechanosensitive molecular clutch drives complement receptor-mediated phagocytosis.

Abstract

αMβ2 integrin (complement receptor 3) is a major receptor for phagocytosis in macrophages. In other contexts, integrins’ activities and functions are mechanically linked to actin dynamics through focal adhesions (FAs). We asked whether mechanical coupling of αMβ2 integrin to the actin cytoskeleton mediates phagocytosis. We found that particle internalization was driven by formation of Arp2/3 and formin-dependent actin protrusions that wrapped around the particle. Focal complex-like adhesions formed in the phagocytic cup that contained β2 integrins, FA proteins and tyrosine kinases. Perturbation of talin and Syk demonstrated that a talin-dependent link between integrin and actin and Syk-mediated recruitment of vinculin enable force transmission to target particles and promote phagocytosis. Altering target mechanical properties demonstrated more efficient phagocytosis of stiffer targets. Thus, macrophages use tyrosine kinase signaling to build a mechanosensitive, talin- and vinculin-mediated, FA-like molecular clutch, which couples integrins to cytoskeletal forces to drive particle engulfment.