Arp2

Arp2, short for actin-related protein 2, is a highly conserved protein that participates in the nucleation of actin filaments. In humans it is encoded by the ACTR2 gene. Arp2 is a core component of the Arp2/3 complex, a seven-subunit assembly that also includes Arp3 and the regulatory subunits ARPC1–ARPC5. The Arp2/3 complex is present in most eukaryotic cells and localizes to actin-rich structures such as lamellipodia and endocytic cups.

Function and mechanism: The Arp2/3 complex catalyzes the formation of branched actin networks. Activation occurs when nucleation-promoting factors (NPFs), such as members of the WASP family (WASP, WAVEs), bind to the complex and recruit it to membranes. Upon activation, Arp2 and Arp3 form a short actin-like nucleus that seeds a new daughter filament growing from the side of an existing mother filament, creating a branch typically at a ~70-degree angle.

Regulation and significance: The activity of Arp2/3 is tightly regulated and essential for processes that rely on rapid cytoskeletal remodeling, including cell migration, adhesion, endocytosis, and vesicle trafficking. Structural studies have revealed the actin-like structure of Arp2 and its conformational changes during activation. Genetic or pharmacological perturbations of Arp2/3 function disrupt motility and morphogenesis in various model systems.

Clinical and research notes: Dysregulation of Arp2/3 activity has been linked to abnormal cell movement and disease in experimental systems, and the complex remains a focus of studies on cancer metastasis, immune cell function, and neuronal development.