Actin is a protein present in the cells of nearly all complex life forms, including animals, plants, and fungi. As one of the most plentiful proteins in many cell types, its primary role is to provide a structural foundation that maintains a cell’s shape and internal organization.
Building the Cell’s Scaffolding: Actin Structure and Polymerization
Actin exists in two states: as individual, globular proteins known as G-actin and as long chains called filamentous or F-actin. The assembly of these filaments, a process called polymerization, requires energy from adenosine triphosphate (ATP). During polymerization, G-actin monomers are strung together like beads to form a structurally robust filament.
These newly formed actin filaments exhibit polarity, meaning they have a “plus” end and a “minus” end. This polarity relates to the rate of growth, as monomers are added more rapidly to the plus end than the minus end. This directional characteristic is important for guiding cell growth and creating tracks along which motor proteins can transport cargo throughout the cell.
Actin filaments are in a constant state of flux, a condition of dynamic instability. This involves a process called treadmilling, where G-actin monomers are added to the plus end while simultaneously being removed from the minus end. This dynamic remodeling allows the cell to rapidly change its shape and internal structure in response to various signals.
Actin in Action: Powering Cellular Processes
The actin cytoskeleton, a dynamic network of filaments, confers mechanical strength and shape to the cell. A dense layer of actin just beneath the cell membrane, the cell cortex, provides structural support and helps the cell resist external pressures. This reinforcement allows cells to maintain distinct shapes, from flat skin cells to intricate neurons.
A primary function of actin is to drive cell motility. Cells crawl and migrate by extending specialized structures at their leading edge. Flat, sheet-like protrusions known as lamellipodia and thin, finger-like extensions called filopodia are pushed forward by the rapid polymerization of actin filaments. This forward extension, followed by the contraction of the cell body, allows movement for processes like immune responses and tissue repair.
In muscle cells, actin filaments are arranged in parallel with another protein, myosin, which functions as a motor. Myosin pulls on the actin filaments, causing them to slide past one another. This sliding action, repeated in countless units throughout a muscle fiber, generates the force required for all muscular movement, from lifting an object to the beating of the heart.
During cell division, actin participates in cytokinesis, the process that separates one cell into two. After the genetic material has been segregated, a ring composed of actin and myosin forms at the cell’s equator. This contractile ring tightens like a drawstring, pinching the cell membrane inward until two independent daughter cells are formed.
The Conductors of the Actin Orchestra: Regulatory Proteins
Actin’s versatility is governed by over 100 different types of actin-binding proteins (ABPs). These regulatory molecules control nearly every aspect of actin’s behavior, dictating where and when filaments are assembled, how they are organized, and how quickly they are taken apart. Through the precise action of ABPs, a cell can construct a wide variety of actin-based structures.
ABPs can be grouped by their specific functions in managing the actin network. Some proteins initiate or modify filament formation, while others organize them into larger structures.
- Nucleators, such as the Arp2/3 complex and formins, initiate the formation of new filaments, creating either branched networks or long, unbranched chains.
- Monomer-binding proteins control the availability of G-actin for polymerization.
- Capping proteins attach to the ends of filaments, preventing them from growing or shrinking.
- Severing proteins chop long filaments into shorter pieces, which can change the consistency of the cytoplasm or create new starting points for filament growth.
- Cross-linking proteins organize filaments into different architectures, such as tight bundles or gel-like networks.
- Motor proteins like myosins use the filaments as tracks for movement, driving processes such as muscle contraction and vesicle transport.
When Actin Goes Awry: Implications for Health and Disease
Defects in actin or its regulatory proteins can lead to a wide range of human diseases. Genetic mutations affecting the actin cytoskeleton can manifest in conditions affecting muscle function, such as certain congenital myopathies and cardiomyopathies. The function of the immune system can also be compromised, as seen in Wiskott-Aldrich syndrome, where immune cells have difficulty migrating.
The integrity of actin structures is also relevant to hearing. The sensory cells of the inner ear rely on highly organized, actin-filled protrusions called stereocilia to detect sound vibrations. Defects in the proteins that organize these structures can lead to congenital deafness. In cancer, the cell motility machinery can be exploited by tumor cells, allowing them to break away from a primary tumor, invade surrounding tissues, and metastasize.
The cellular actin network is also a target for infectious pathogens. Certain bacteria, such as Listeria monocytogenes, harness the host cell’s actin polymerization machinery. By recruiting actin to their surface, these bacteria build comet-like tails that propel them through the cytoplasm and into adjacent cells, spreading the infection. Similarly, some viruses, like the vaccinia virus, exploit the actin cytoskeleton to facilitate their movement within and between cells.