Just beneath the outer membrane of an animal cell lies a dynamic and dense network of protein filaments known as the cortical actin cytoskeleton. This specialized layer, often called the cell cortex, is composed primarily of actin proteins and functions as a modulator of the cell’s surface properties and overall behavior. It acts as both a scaffold and a muscle, providing mechanical support to maintain and alter the cell’s form while generating forces for various cellular activities. The cortical actin network gives the cell its physical integrity, helping it resist external pressures. This layer is not a static structure but a highly plastic one, constantly remodeling itself to meet the cell’s needs and how it interacts with its environment, moves, and divides.
Building the Cell’s Edge: Structure of Cortical Actin
The fundamental building block of the cortical actin network is the actin filament, a thin and flexible protein structure. These filaments are organized into a dense, cross-linked meshwork that lies directly beneath the cell’s plasma membrane. The architecture of this network can vary depending on the cell type and its physiological state, but it provides a combination of rigidity and flexibility to the cell surface.
This intricate web is not composed of actin alone; its organization and function depend on many actin-binding proteins (ABPs). These proteins perform a variety of roles, such as linking actin filaments to each other and anchoring the network to the plasma membrane. For instance, cross-linking proteins like filamin help organize the filaments into a random network, while bundling proteins such as fascin align them into parallel stacks.
Motor proteins, most notably non-muscle myosin II, also contribute to the network’s function. These proteins use cellular energy to pull on actin filaments, which generates tension and allows the cortex to contract. This contractility enables the cortex to drive changes in cell shape. The entire structure is tethered to the inner face of the cell membrane by another class of proteins, ensuring the network and the membrane function as a single, cohesive unit.
Fundamental Cellular Activities Driven by Cortical Actin
This network is central to cell migration, a process for development and immune surveillance. For a cell to move, it must extend protrusions in the direction of travel, such as broad, sheet-like lamellipodia or thin, finger-like filopodia. The assembly of actin filaments at the leading edge powers the formation of these structures, pushing the cell membrane forward. In some forms of movement, contractions within the cortex create hydrostatic pressure that can cause the membrane to bulge out in a process called blebbing.
During cell division, or cytokinesis, cortical actin performs a distinct role. After the genetic material has been duplicated and separated, a contractile ring composed of actin and myosin II assembles at the cell’s equator. This ring progressively tightens, pinching the cell membrane inward until the cell is cleaved in two.
The cortex also facilitates the transport of materials into and out of the cell through endocytosis and exocytosis. It helps regulate the formation and movement of vesicles, which are small membrane-bound sacs that carry substances. The dynamic remodeling of the actin network at the cell surface is necessary to create the membrane curvature needed to engulf materials or to allow vesicles to fuse with the membrane for release.
The Dynamic Nature of Cortical Actin
The cortical actin network is far from static; it is in a constant state of flux, with its protein components undergoing rapid turnover. This dynamism is rooted in the processes of actin polymerization and depolymerization—the assembly and disassembly of actin filaments. Individual actin monomers can be quickly added to the ends of existing filaments to make them longer or removed to make them shorter, allowing the network to be remodeled in seconds.
This turnover is not random but is regulated by a complex interplay of signaling pathways and actin-binding proteins that control where and when assembly and disassembly occur. Proteins like formins promote the growth of long, linear filaments, while the Arp2/3 complex creates branched networks. Conversely, proteins such as cofilin work to break down filaments, promoting their disassembly. The balance between these opposing activities is controlled by the cell in response to both internal and external signals.
Impact on Health and Disease
The proper functioning of the cortical actin network is implicated in numerous human diseases when it is dysregulated. In cancer, changes to the actin cytoskeleton are a feature of metastasis, the process by which cancer cells spread. To metastasize, a cancer cell must become migratory and invasive, abilities that are dependent on the reorganization of cortical actin. Alterations in the expression of actin-regulating proteins can make cancer cells more mobile, allowing them to break away from the primary tumor and enter the bloodstream. For example, the formation of actin-rich protrusions called invadopodia enables cancer cells to degrade the extracellular matrix, clearing a path for their invasion.
Disruptions in cortical actin also have effects on the immune system. Immune cells rely on their ability to change shape and migrate to patrol the body and respond to pathogens. Defects in the actin cytoskeleton can impair the function of immune cells like macrophages and neutrophils, affecting their ability to move to sites of infection. This can lead to immunodeficiency or to autoimmune and autoinflammatory diseases.
Furthermore, because cortical actin is important for cell division and shape changes, it plays a role in embryonic development. The coordinated movements of cells that form tissues and organs are driven by the forces generated by the actin cytoskeleton. Mutations in genes that code for actin or its regulatory proteins can lead to a range of developmental abnormalities.