Actin is a highly abundant and fundamental protein found in nearly all eukaryotic cells, from yeast to humans. It forms a versatile internal framework, often likened to a cellular “jack-of-all-trades,” supporting a wide array of life-sustaining processes. This protein is remarkably conserved across diverse species, with human actin sharing approximately 87% similarity with yeast actin and 80% with actin from amoebae, highlighting its ancient importance.
Assembling Actin Filaments
Actin exists in two primary forms: globular actin (G-actin), the individual protein subunit, and filamentous actin (F-actin), the long chain formed when these subunits link together. This transformation can be visualized like individual Lego bricks (G-actin) clicking together to form a long beam (F-actin). This assembly process, termed polymerization, involves G-actin monomers, each binding an ATP molecule, adding to the growing ends of an F-actin filament, particularly at the faster-growing “plus end.”
The F-actin filament forms a tight, right-handed double helix structure, approximately 7 nanometers in diameter. Once integrated into the filament, the ATP bound to each actin subunit is hydrolyzed into ADP and phosphate, which influences filament stability. This polymerization is a dynamic and reversible process, allowing the cell to rapidly build up and break down actin structures as needed, ensuring flexibility in cellular functions.
Providing Cellular Structure
Actin plays a static role in providing the cell with its internal architecture, serving as a primary component of the cytoskeleton. This cytoskeleton acts as the cell’s internal scaffolding, much like a tent’s poles. Networks of actin filaments are concentrated just beneath the cell’s outer membrane, forming a structure called the cell cortex.
This network of actin filaments provides mechanical support, helping the cell maintain its shape and resist external pressures. The organized arrangement of these filaments allows cells to resist deformation and maintain integrity. The connection of the actin cytoskeleton to the plasma membrane is important for cell structure and function.
Powering Biological Movement
Actin’s dynamic nature is evident in its role in powering various forms of biological movement, from the contraction of large muscles to the subtle crawling of individual cells. A key function involves its partnership with myosin in muscle contraction. This process is explained by the “sliding filament model,” where thin actin filaments slide past thick myosin filaments.
In muscle cells, myosin II proteins possess heads that bind to actin filaments, forming temporary connections called cross-bridges. Myosin then hydrolyzes ATP to pull on the actin filaments. This pulling action shortens the sarcomere, the functional unit of muscle, without the individual actin or myosin filaments changing length.
This cycle of myosin binding, pulling, and detaching drives the shortening of muscle fibers, generating force for all voluntary movements, including walking and lifting, as well as involuntary actions like breathing and the rhythmic beating of the heart. The coordination of these sliding interactions allows for powerful muscle contractions.
Beyond muscle, actin also enables the movement of non-muscle cells, such as immune cells or fibroblasts, through a process often described as “crawling.” These cells extend protrusions like lamellipodia or filopodia at their leading edge. This extension is driven by the localized assembly of actin filaments.
New actin monomers are added to the growing ends of existing filaments, pushing the cell membrane forward. This continuous polymerization generates the force required for the cell to migrate across surfaces. As the cell moves forward, older actin filaments at the rear are disassembled, and their components are recycled for new growth at the front, creating a dynamic cycle of protrusion and retraction.
Enabling Cell Division
Actin plays an important role in the final stage of cell division, known as cytokinesis. After genetic material is duplicated and separated, actin, with myosin II, forms a structure called the contractile ring. This ring assembles in the middle of the dividing cell.
The contractile ring is composed of filamentous actin and myosin II, linked to the plasma membrane. As cell division progresses, the myosin motors within this ring pull on the actin filaments. This action causes the ring to tighten and constrict.
The constriction of the contractile ring creates a deepening indentation on the cell surface, known as the cleavage furrow. This furrow pinches the cell into two genetically identical daughter cells, ensuring the accurate distribution of cellular components.
When Actin Fails
Given actin’s fundamental involvement in numerous cellular processes, any malfunction can have significant consequences for human health. Mutations in the genes that encode actin can lead to a range of severe disorders, particularly those affecting muscle structure and function. These conditions stem from issues with actin filament formation, stability, or interaction with other proteins.
One group of disorders is congenital myopathies, diseases affecting skeletal muscles from birth. For example, actin-accumulation myopathy is caused by mutations in the ACTA1 gene, which codes for skeletal alpha-actin. These mutations can impair the binding of actin to ATP, leading to abnormal thin filament formation and severe muscle weakness, poor muscle tone, and breathing difficulties.
Another category of diseases linked to actin dysfunction includes cardiomyopathies, conditions affecting the heart muscle. Mutations in the ACTC1 gene, which produces cardiac alpha-actin, are a common cause of heart disease. These mutations can lead to conditions such as hypertrophic cardiomyopathy (HCM), where the heart muscle thickens, or dilated cardiomyopathy (DCM), where the heart chambers enlarge and weaken.