Formation of Membrane Domains via Actin Waves: A Fundamental Principle in the Generation of Dynamic Structures in Phagocytes.

Phagocytes carry out their functions by organizing new subcellular structures. During phagocytosis, macrophages internalize and degrade pathogens and apoptotic cells by forming the phagocytic cup and phagosome. Osteoclasts resorb bone by forming the sealing zone and ruffled border at the ventral membrane. This review explores the organizational principles of these dynamic structures. In in vitro frustrated phagocytosis, specifically 2D phagocytosis by macrophages, the activation of the Fcγ receptor generates multiple self-organized waves containing F-actin, Arp2/3, and phosphoinositides. The propagation of these circular actin waves segregates the inside from the outside, leading to the compartmentalization of the ventral membrane. As the actin wave passes, cortical actin is disrupted, and membrane remodeling occurs within the wave, creating a new membrane domain with high exocytic activity. These processes mirror the formation of the constriction zone in the phagocytic cup and phagosome during 3D phagocytosis. A similar mechanism may also contribute to the formation of the sealing zone and ruffled border in osteoclasts. Based on these observations, we propose that dynamic structures formed from actin waves are organized through the fractal integration of self-organized, oscillatory substructures, with F-actin treadmilling fueling their formation and maintenance.