Shaping cups into phagosomes and macropinosomes

• Published in: Nature reviews. Molecular cell biology Vol. 9; no. 8; pp. 639 - 649
• Main Author: Swanson, Joel A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2008; Nature Publishing Group
• Subjects: Actin; Animals; Biochemistry; Biomedical and Life Sciences; Cancer Research; Cell activation; Cell Biology; Cell membranes; Cell Physiological Phenomena; Cell receptors; Cell Shape - physiology; Cell surface; Cups; Cytology; Cytoskeleton; Developmental Biology; Feedback; Feedback, Physiological - physiology; Humans; Immunoglobulins; Ingestion; Invaginations; Life Sciences; Ligands; Membrane fusion; Membrane vesicles; Membranes; Models, Biological; Molecular dynamics; Neutrophils; Particle shape; Phagocytes; Phagocytosis; Phagocytosis - physiology; Phagosomes; Phagosomes - physiology; Phagosomes - ultrastructure; Phospholipids; Physical properties; Physiological aspects; Pinocytosis - physiology; Plasma; Proteins; Receptors; review-article; Signal transduction; Signal Transduction - physiology; Signaling; Solutes; Stem Cells; Stiffness; Vesicle fusion; Vesicles; United States
• ISSN: 1471-0072; 1471-0080; 1471-0080
• DOI: 10.1038/nrm2447

Key Points Phagocytosis is the ingestion by cells of particles or other cells. Receptors in membranes of phagocytic cells organize the advance of the plasma membrane and the actin cytoskeleton around target particles, forming intracellular membrane-bounded compartments called phagosomes. Macropinocytosis is the ingestion by cells of extracellular solutes and fluid into 0.2–10-μm diameter vesicles, or macropinosomes. Macropinosomes can form spontaneously or in response to activation of cell-surface receptors. Common signalling mechanisms organize the construction of phagocytic or macropinocytic cup-shaped invaginations of the plasma membrane. Receptors, GTPases of the Ras superfamily and membrane phospholipids regulate the component activities of actin-filament assembly, disassembly and contraction, as well as the fusion of membrane vesicles with cup membranes. Imaging of molecular dynamics in living cells indicates that phagocytic and macropinocytic cups exhibit distinct patterns of signalling that correspond to the early and late stages of their formation. Activated receptor complexes (short-range signals) generate diffusible signal molecules (medium-range signals) that are subject to feedback regulation and that, at suprathreshold concentrations, can activate transitions from early to late stages of signalling. Phospholipids generated in the confines of a forming cup integrate and amplify signalling in that region of the membrane. Receptor-mediated signal transduction for phagocytosis and macropinocytosis is modulated by cell structure and is conditional on feedback regulation that is related to cup integrity, particle stiffness and particle shape. The ingestion of particles or cells by phagocytosis and of fluids by macropinocytosis requires cup-shaped invaginations of the plasma membrane. Common signalling mechanisms and distinct signalling patterns characterize the different stages of the formation of phagocytic and macropinocytic cups. The ingestion of particles or cells by phagocytosis and of fluids by macropinocytosis requires the formation of large endocytic vacuolar compartments inside cells by the organized movements of membranes and the actin cytoskeleton. Fc-receptor-mediated phagocytosis is guided by the zipper-like progression of local, receptor-initiated responses that conform to particle geometry. By contrast, macropinosomes and some phagosomes form with little or no guidance from receptors. The common organizing structure is a cup-shaped invagination of the plasma membrane that becomes the phagosome or macropinosome. Recent studies, focusing on the physical properties of forming cups, indicate that a feedback mechanism regulates the signal transduction of phagocytosis and macropinocytosis.