Actin is an abundant protein in eukaryotic cells (cells with a nucleus). It exists as individual molecules, G-actin, that link together to form long chains called F-actin. These filaments are a component of the cell’s internal framework, the cytoskeleton. The process of starting a new actin filament from these monomers is called actin nucleation. This initial step is the most regulated part of constructing the actin structures cells rely on for various functions.
The Importance of Starting Actin Filaments
The controlled initiation of actin filaments is a fundamental process for cellular life. Without assistance, assembling the first few actin monomers into a stable “seed” or nucleus is a slow step known as the lag phase. This occurs because small, unstable groupings of actin molecules tend to fall apart before they can grow. Cells use specialized molecular machinery to accelerate this step, allowing for rapid construction of actin filaments when and where they are needed.
This rapid and targeted filament formation is foundational to many cellular activities. It enables cells to move and crawl, which relies on the quick assembly of actin networks at the cell’s leading edge. The ability to change shape and maintain structural integrity also depends on the dynamic actin cytoskeleton. Actin filaments also form tracks for internal transport and play a role in cell division, a process called cytokinesis.
How Cells Initiate Actin Filament Growth
Cells use proteins known as actin nucleators to start the formation of new filaments. These proteins overcome the initial kinetic barrier of nucleation, which is otherwise suppressed by proteins that bind to individual actin monomers. The two most prominent families of nucleators are the Arp2/3 complex and formins, which build distinct actin structures through different mechanisms.
The Arp2/3 complex is a group of proteins that serves as a template for a new filament when activated. It binds to the side of a pre-existing actin filament and initiates a new one at a 70-degree angle, resulting in branched, web-like actin networks. The activation of the Arp2/3 complex is a regulated event, triggered by proteins like WASP or WAVE. These branched networks are found at the leading edge of mobile cells in structures called lamellipodia, pushing the cell membrane forward.
In contrast, proteins from the formin family create long, unbranched actin filaments. Formins stabilize an initial pair of actin molecules and remain attached to the fast-growing end of the filament as it lengthens. This attachment allows for the rapid addition of new actin monomers, delivered by proteins like profilin. These linear filaments are integral to structures like filopodia (thin, finger-like projections from the cell surface) and stress fibers (contractile bundles). Formins also help assemble the contractile ring used in cell division.
Controlling Actin Assembly and Its Implications
Actin nucleation is not a random process; it is controlled by the cell in both time and location. This regulation is achieved through signaling pathways that activate or deactivate nucleating proteins in response to various cues. Cells also control where filaments are built by localizing the nucleators or their activating proteins to specific areas. The availability of actin monomers is another layer of control.
When this regulation of actin nucleation fails, it can have significant consequences. Errors in the process are linked to human diseases, including immune system disorders where cell motility is affected. In cancer, abnormal actin nucleation can enhance the ability of tumor cells to move and invade surrounding tissues, a step in metastasis. Some infectious pathogens also hijack a host cell’s actin machinery, building “comet tails” to propel them through the cytoplasm and into adjacent cells.