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

Developmental cell (2019-06-25)
Philip P Ostrowski, Spencer A Freeman, Gregory Fairn, Sergio Grinstein
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.