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.
Plasmodium falciparum circumsporozoite protein (CSP) is a critically required abundant surface protein of sporozoites and a major vaccine candidate. However, neither the structure nor the role of CSP in sporozoite motility is well understood. Our recent in vitro data, from single molecule pulling experiments suggested a mechanically pliable structure for P. falciparum CSP. By engineering vegetative cells of the cellular slime mold Dictyostelium discoideum with regulatable CSP surface expression, we report evidence for direct involvement of CSP towards conferring elastic properties and motility of the cells. With an increase in the surface CSP levels by 5to8 fold, the Youngs moduli of the cells, observed through atomic force microscopy, decreased around 2 fold, with a concomitant increase in motility by about 2 fold. Interestingly, only full length CSP expression conferred maximal flexibility and motility, as opposed to repeat region alone or the flanking domains of CSP. The enhanced motility of the CSP expressing cells was abrogated with anti CSP antibodies as well as phospholipase cleavage of CSP, indicating specific contribution of CSP towards motility. Measurements of the Youngs moduli of Plasmodium berghei midgut (MG) and salivary gland (SG) sporozoites revealed an inverse correlation with CSP levels with a decrease from 1.1 kPa to 0.3 kPa as the CSP concentration doubled from MG to SG sporozoites. We hypothesize that high CSP level lowers the stiffness of sporozoites possibly through its pliable surface-coat, leading to cellular flexibility. These findings may explain a sporozoites developmental ability to enhance its CSP levels during transition from midgut to salivary glands to suit a migratory mode in the host, needed for successful hepatocyte invasion.
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, also co-localises with actin at the phagocytic cup in the early stages of phagocytosis. Both knockdown and overexpression of Lis1 perturbs phagocytosis, suggesting that an optimum level of Lis1 is required to regulate actin dynamics within the phagocytic cup during particle engulfment. 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, a general role for Lis1 in regulating actin dynamics is suggested by observing defective migration of cells overexpressing Lis1. Taken together, Lis1 localises to the phagocytic cup and influences actin dynamics in a manner that is important for the uptake of solid particles in cells.
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