The cytoskeleton in phagocytosis and macropinocytosis
Sivakami Mylvaganam1, Spencer A Freeman1, Sergio Grinstein1
1Program in Cell Biology, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Abstract:
Cells of the innate immune system, notably macrophages, neutrophils and dendritic cells, perform essential antimicrobial and homeostatic functions. These functions rely on the dynamic surveillance of the environment supported by the formation of elaborate membrane protrusions. Such protrusions - pseudopodia, lamellipodia and filopodia - facilitate the sampling of the surrounding fluid by macropinocytosis, as well as the engulfment of particulates by phagocytosis. Both processes entail extreme plasma membrane deformations that require the coordinated rearrangement of cytoskeletal polymers, which exert protrusive force and drive membrane coalescence and scission. The resulting vacuolar compartments undergo pronounced remodeling and ultimate resolution by mechanisms that also involve the cytoskeleton. Here, we describe the regulation and functions of cytoskeletal assembly and remodeling during macropinocytosis and phagocytosis.
Insights
Innate immune cells use dynamic membrane protrusions like pseudopodia for phagocytosis and macropinocytosis. Cytoskeletal remodeling drives these processes and vacuolar compartment resolution.
Area of Science:
- Cell Biology
- Immunology
- Biochemistry
Background:
- Innate immune cells, including macrophages, neutrophils, and dendritic cells, are crucial for host defense and tissue homeostasis.
- Their functions depend on sensing the environment through membrane protrusions, such as pseudopodia, lamellipodia, and filopodia.
- These structures mediate the uptake of fluids (macropinocytosis) and particles (phagocytosis).
Purpose of the Study:
- To elucidate the regulation and functions of cytoskeletal dynamics during macropinocytosis and phagocytosis.
- To understand how cytoskeletal assembly and remodeling contribute to membrane deformation and vacuolar compartment formation and resolution.
Main Methods:
- The study focuses on the cytoskeletal mechanisms underlying cellular processes.
- It involves observing membrane dynamics and cytoskeletal rearrangements during phagocytosis and macropinocytosis.
Main Results:
- Cytoskeletal polymers undergo coordinated rearrangements to generate forces for membrane protrusions.
- These rearrangements are essential for plasma membrane deformation during macropinocytosis and phagocytosis.
- The cytoskeleton also plays a key role in the remodeling and resolution of vacuolar compartments formed by these processes.
Conclusions:
- Cytoskeletal assembly and remodeling are fundamental to the cellular processes of macropinocytosis and phagocytosis.
- These dynamic cytoskeletal events enable innate immune cells to perform essential antimicrobial and homeostatic functions.
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