Arp2/3 complex

Arp2/3 complex is a seven-subunit protein complex that plays a crucial role in the regulation of the actin cytoskeleton. The complex is composed of two actin-related proteins, Arp2 and Arp3, and five other subunits, ARPC1-ARPC5. It is involved in the nucleation of new actin filaments and the formation of branched actin networks, making it essential for a variety of cellular processes including cell motility, endocytosis, and the maintenance of cell shape.

Structure and Function

The Arp2/3 complex has a unique structure that allows it to bind to the sides of existing actin filaments and initiate the growth of new filaments at a 70-degree angle. This branching mechanism is critical for the formation of dense actin networks within cells. The activation of the Arp2/3 complex is tightly regulated by nucleation-promoting factors (NPFs), such as the Wiskott-Aldrich syndrome protein (WASP) and the WASP-family verprolin-homologous protein (WAVE), which bind to the complex and stimulate its actin-nucleating activity.

Regulation

The activity of the Arp2/3 complex is regulated by several mechanisms, including phosphorylation, the binding of ATP/ADP, and interactions with other proteins. Inactive Arp2/3 complex can be activated by NPFs, which induce conformational changes that allow the complex to bind to actin filaments and nucleate new branches. Additionally, the complex can be inhibited by proteins such as Arpin and Coronin, which modulate its activity in response to cellular signals.

Cellular Functions

The Arp2/3 complex is involved in various cellular functions that require the remodeling of the actin cytoskeleton. In cell motility, the complex generates branched actin networks at the leading edge of moving cells, providing the force for cell movement. In endocytosis, it facilitates the formation of actin patches around vesicles, aiding in their internalization. The complex also plays a role in the maintenance of cell shape and the formation of cellular structures such as lamellipodia and filopodia.

Clinical Significance

Given its role in cell motility and other critical cellular processes, the Arp2/3 complex has been implicated in various diseases, including cancer, where alterations in cell movement and invasion are key features. Inhibitors of the Arp2/3 complex are being explored as potential therapeutic agents for cancer and other diseases characterized by abnormal cell migration and invasion.

Research Tools

The study of the Arp2/3 complex has been facilitated by various biochemical and molecular biology tools. These include the use of small molecule inhibitors, genetic knockdown or knockout techniques, and the development of fluorescent probes to visualize the complex and its activity in living cells.