The Arp2/3 complex is a protein assembly found within nearly all eukaryotic cells. This complex plays a role in establishing cell shape and driving cellular movement. It contributes to the internal organization of cells and their ability to interact with their surroundings.
Unveiling the Arp2/3 Complex
The Arp2/3 complex consists of seven distinct subunits. These include two actin-related proteins, Arp2 and Arp3, along with five other proteins called ARPC proteins (ARPC1, ARPC2, ARPC3, ARPC4, and ARPC5). These subunits are evolutionarily conserved across diverse eukaryotic organisms.
Arp2 and Arp3 are structurally similar to monomeric actin, serving as initiation points for new actin filaments. The complex is found in dynamic regions of the actin cytoskeleton, such as near the cell membrane in lamellipodia and within the cytoplasm. This localization supports its role in orchestrating changes in cell shape and movement.
How the Arp2/3 Complex Builds Cellular Scaffolds
The primary function of the Arp2/3 complex is to initiate the formation of new actin filaments, a process called nucleation, and to create branched networks. The complex is activated by proteins called nucleation-promoting factors (NPFs) and binds to the side of an existing actin filament, the “mother” filament. This binding positions Arp2 and Arp3 to form the base of a new “daughter” filament.
The new actin filament grows at a characteristic 70-degree angle from the side of the mother filament. This branching leads to a tree-like, dendritic network of actin filaments. This rapid and organized assembly of branched actin structures is crucial for generating pushing forces and facilitating movement within the cell. The Arp2/3 complex remains associated with the pointed (slow-growing) end of the newly formed daughter filament.
Essential Roles in Cell Function
The actin structures built by the Arp2/3 complex are involved in numerous cellular activities requiring changes in cell shape and movement. A role is in cell migration, where the complex helps push out the leading edge of a cell, forming lamellipodia. This activity is important for processes such as immune cell trafficking, wound healing, and embryonic development.
The complex also participates in endocytosis, the process by which cells engulf substances from their surroundings. It facilitates the dynamic changes in the plasma membrane necessary for vesicle formation and internalization. Arp2/3 is also involved in phagocytosis, where immune cells engulf pathogens or cellular debris by forming actin-rich cups around the target. During cell division, cytokinesis, the Arp2/3 complex contributes to the formation of the contractile ring that divides the parent cell into two daughter cells.
When the Arp2/3 Complex Goes Awry
Dysregulation of the Arp2/3 complex can have consequences for cellular function and contribute to disease. Its overactivity can promote uncontrolled cell migration, a characteristic feature of cancer metastasis. Enhanced Arp2/3 activity can enable cancer cells to move more aggressively and invade surrounding tissues.
Pathogens can also exploit the Arp2/3 complex to facilitate their movement and spread within a host. Listeria monocytogenes uses its protein ActA to activate the host cell’s Arp2/3 complex. This drives actin “comet tails” behind the bacteria, propelling them through the cytoplasm and into neighboring cells. Shigella bacteria recruit the host protein N-WASP, which activates Arp2/3 for actin-based motility.