Actin filaments are fundamental components within nearly all eukaryotic cells, forming a dynamic internal framework known as the cytoskeleton. This intricate network acts like the cell’s internal scaffolding, providing structural support and enabling various cellular activities. These protein structures contribute to a wide range of processes, from maintaining cellular architecture to facilitating movement.
The Structure of an Actin Filament
An actin filament, also known as a microfilament, is a polymer composed of individual protein subunits. These subunits are globular actin, or G-actin, which assemble into filamentous F-actin. Each filament typically has a diameter of approximately 7 nanometers and exhibits a distinct two-stranded helical arrangement.
A defining characteristic of an actin filament is its inherent polarity, meaning its two ends are structurally different. One end is known as the “plus” end, also called the barbed end, while the opposite is the “minus” end, or pointed end. This polarity dictates the directionality and rates at which actin subunits are added or removed, a property that is fundamental to the filament’s dynamic functions.
How Actin Filaments Are Assembled
Actin filaments constantly undergo assembly (polymerization) and disassembly (depolymerization). G-actin monomers, often bound to ATP, primarily add onto the fast-growing plus end. Conversely, monomers, bound to ADP after ATP hydrolysis within the filament, are more readily removed from the slower-growing minus end. This continuous addition at one end and removal at the other, even while the filament maintains a relatively stable length, is termed treadmilling.
Numerous actin-binding proteins regulate these dynamic processes. Proteins such as profilin can enhance the rate of G-actin addition to the plus end, while cofilin can promote depolymerization from the minus end and even sever filaments into shorter fragments. Other proteins, like the Arp2/3 complex and formins, initiate the formation of new filaments or branches. Cross-linking proteins such as fascin or filamin A organize individual filaments into larger, more complex structures like bundles or networks, tailoring the actin cytoskeleton for diverse cellular roles.
The Role of Actin in Cell Movement
Cellular movement, such as cell crawling, relies heavily on the dynamic behavior of actin filaments. At the leading edge of a moving cell, actin polymerization pushes against the cell membrane, driving outward extension. This process forms sheet-like protrusions called lamellipodia or slender, finger-like extensions known as filopodia, which help the cell explore and establish new contacts.
The motor protein myosin works in conjunction with actin to generate contractile forces for cell locomotion. Myosin molecules “walk” along actin filaments, pulling them past one another in a mechanism similar to muscle contraction. This contractile activity, often occurring behind the advancing front, pulls the main body of the cell forward, coordinating the extension and retraction phases of cell crawling.
Actin’s Function in Cell Shape and Division
Beyond cell movement, actin filaments maintain cell shape and facilitate cell division. Just beneath the cell membrane, actin filaments form a dense network, the cell cortex. This cortical network provides mechanical support, contributing to structural integrity and allowing resistance to external forces while maintaining form.
During cytokinesis, the final stage of cell division, actin filaments are instrumental in physically separating the two newly formed daughter cells. A specialized structure, the contractile ring, assembles at the cell’s equator. This ring is composed of actin filaments and myosin-II, and its constriction, much like tightening a purse-string, creates a cleavage furrow that progressively pinches the cell in half, ensuring complete division of the cytoplasm.
When Actin Goes Wrong
Disruptions in actin filament function can have serious consequences for cellular health and contribute to various diseases. In cancer, for instance, dysregulation of the actin cytoskeleton is a hallmark of metastasis. Cancer cells exploit their actin machinery to become mobile, detaching from primary tumors, invading surrounding tissues, and spreading to distant sites.
Certain pathogens have also evolved mechanisms to hijack actin dynamics for survival and spread. The bacterium Listeria monocytogenes, for example, manipulates host cell actin polymerization to propel itself through the cytoplasm and into neighboring cells, avoiding the immune system. These instances highlight the delicate balance of actin regulation and the impact when disturbed.