Lis1 co-localizes with actin in the phagocytic cup and regulates phagocytosis.

Phagocytosis, the ingestion of solid particles by cells is essential for nutrient uptake, innate immune response, antigen presentation and organelle homeostasis. Here we show that Lissencephaly-1 (Lis1), a well-known regulator of the microtubule motor dynein, co-localizes with actin at the phagocytic cup in the early stages of phagocytosis. Both knockdown and overexpression of Lis1 perturb phagocytosis, suggesting that Lis1 levels may be regulated during particle engulfment to facilitate remodeling of actin filaments within the phagocytic cup. This requirement of Lis1 is replicated in mouse macrophage cells as well as in the amoeba Dictyostelium, indicating an evolutionarily conserved role for Lis1 in phagocytosis. In support of these findings, Dictyostelium cells overexpressing Lis1 show defects in migration possibly caused by dysregulated actin. Taken together, Lis1 localizes to the phagocytic cup and influences the actin cytoskeleton in a manner that appears important for the uptake of solid particles into cells.