Actin polymerization is a fundamental biological process where individual protein units assemble into larger, filament-like structures. This dynamic assembly and disassembly of actin proteins is central to many cellular activities, allowing cells to adapt and respond to their environments.
How Actin Filaments Form
Actin exists in two forms: globular actin (G-actin) monomers and filamentous actin (F-actin) polymers. G-actin monomers are the building blocks that form F-actin filaments. Each G-actin monomer has binding sites, allowing it to interact with others in a head-to-tail fashion to form a double-stranded helix.
The formation of actin filaments from G-actin monomers proceeds through three phases. The first phase, nucleation, involves the initial formation of a stable “nucleus” or seed. Following nucleation, the elongation phase begins with the rapid addition of G-actin monomers to both ends of the growing filament. Monomers add faster to one end, termed the “plus” or “barbed” end, compared to the “minus” or “pointed” end.
The third phase is the steady state, where monomer addition and filament disassembly rates become balanced. This equilibrium is influenced by ATP hydrolysis, which occurs as G-actin monomers are incorporated into the filament. This ATP hydrolysis contributes to treadmilling, a phenomenon where there is a net addition of monomers at the plus end and a net loss at the minus end, even at steady state.
Regulating Actin Assembly
Cells exert precise control over actin polymerization, enabling them to rapidly reconfigure their internal structures. This regulation is achieved through various actin-binding proteins that influence different stages of filament assembly and disassembly. These proteins ensure that actin structures form exactly where and when they are needed.
Nucleation-promoting factors, such as the Arp2/3 complex and formins, play a role in initiating new actin filaments or promoting their growth. The Arp2/3 complex creates branched actin networks, while formins facilitate the formation of long, straight filaments. Capping proteins bind to the ends of actin filaments, preventing further monomer addition or loss and thereby stabilizing the filament length.
Severing proteins cut existing actin filaments into shorter pieces, increasing the number of free ends available for new polymerization or depolymerization. This action contributes to the rapid remodeling of the actin network. Cross-linking proteins organize individual actin filaments into larger, more complex structures, such as bundles found in stress fibers or intricate networks seen in the cell cortex.
Actin’s Cellular Functions
Actin filaments contribute to cell shape and provide structural support, forming a dense network known as the cell cortex. This cortical actin determines the cell’s stiffness and shape. It also helps in transducing mechanical signals from the cell’s exterior to its interior.
Cell movement relies on controlled actin polymerization, especially in processes like amoeboid movement and the migration of cells during wound healing or immune responses. Cells extend protrusions, such as lamellipodia and filopodia, by polymerizing actin at their leading edges. These dynamic extensions allow cells to explore their environment and move across surfaces.
Muscle contraction is another function, where actin filaments interact with myosin motor proteins in a sliding filament mechanism. This organized interaction within muscle cells generates the force required for muscle shortening. During cell division, actin forms a contractile ring that constricts the cell during cytokinesis.
Actin also guides intracellular transport, serving as tracks for the movement of vesicles and organelles within the cell. Motor proteins like myosin move along these actin tracks, transporting cargo to specific destinations. Actin filaments are involved in cell adhesion, forming connections that link cells to each other and to the extracellular matrix.
Implications of Dysfunctional Actin
Disruptions in the precise control of actin polymerization can have consequences for cell function and organismal health. When the dynamic balance of assembly and disassembly is disturbed, cells may lose their ability to maintain shape, move properly, or divide effectively. These impairments can manifest in various pathological conditions.
In cancer, altered actin dynamics contribute to uncontrolled cell proliferation and metastasis, where cancer cells migrate and invade surrounding tissues. The ability of cancerous cells to change shape and move through tissues is often linked to dysfunctional actin regulation. Muscular dystrophies arise from defects in actin-binding proteins, compromising the structural integrity and function of muscle fibers.
Many pathogens, including bacteria and viruses, exploit or manipulate the host cell’s actin cytoskeleton to facilitate their entry, movement within the cell, and spread to neighboring cells. Understanding these dysfunctions provides insights into disease mechanisms and potential therapeutic targets.