Dynamic Podosome-Like Structures in Nascent Phagosomes Are Coordinated by Phosphoinositides

Abstract

Phagocytosis, the engulfment of particulate matter, requires the coordinated polymerization of F-actin; however, the nature and dynamics of the F-actin structures generated during the process are incompletely defined. Using super-resolution microscopy, we observed the formation of podosome-like structures during Fc receptor-mediated phagocytosis. Unlike conventional podosomes, these structures are short lived and vectorial, expanding radially from the sites where phagocytic targets are initially engaged. The expanding ring of podosome-like structures requires the localized formation of PtdIns(3,4,5)P₃. Concomitantly, the initial podosome-like structures disappear from the center of the phagocytic cup, enabling membrane bending around the target. This coordinated disappearance is mediated by localized hydrolysis of PtdIns(4,5)P₂ at the center of the cup. Interference reflection microscopy revealed that the podosome-like structures attach tightly to the target, facilitating the progressive engagement and activation of phagocytic receptors, creating a diffusion barrier and serving as support for the extension of exploratory lamellipodia that probe the target surface.

Keywords: Arp2/3; PI(3,4,5)P3; PI(4,5)P2; integrin; phagocytosis; phosphoinositide; podosome.