Abstract

The actin cytoskeleton is fundamental for the innate immune process of phagocytosis. This study shows that LSP1 plays a pivotal role in the regulation of actin cytoskeleton remodeling during Fcγ receptor–mediated phagocytosis and that its interactions with myosin1e and actin are crucial for the efficiency of this actin-driven process.Actin cytoskeleton remodeling is fundamental for Fcγ receptor–driven phagocytosis. In this study, we find that the leukocyte-specific protein 1 (LSP1) localizes to nascent phagocytic cups during Fcγ receptor–mediated phagocytosis, where it displays the same spatial and temporal distribution as the actin cytoskeleton. Down-regulation of LSP1 severely reduces the phagocytic activity of macrophages, clearly demonstrating a crucial role for this protein in Fcγ receptor–mediated phagocytosis. We also find that LSP1 binds to the class I molecular motor myosin1e. LSP1 interacts with the SH3 domain of myosin1e, and the localization and dynamics of both proteins in nascent phagocytic cups mirror those of actin. Furthermore, inhibition of LSP1–myosin1e and LSP1–actin interactions profoundly impairs pseudopodial formation around opsonized targets and their subsequent internalization. Thus the LSP1–myosin1e bimolecular complex plays a pivotal role in the regulation of actin cytoskeleton remodeling during Fcγ receptor–driven phagocytosis.