Archive for February, 2013


Posted: February 15, 2013 in Uncategorized
Figure 1. The Actin-related protein 2/3 complex (Arp2/3).

Figure 1. The Actin-related protein 2/3 complex (Arp2/3) – click to view animation in secondary tab.

Full protein name: actin-related protein 2/3 complex
Abbreviation: Arp2/3

activation of the arp2/3 complex via the WASP and Scar/WAVE nucleation promoting factors

Figure 2. Activation of the arp2/3 complex via the WASP and Scar/WAVE nucleation promoting factors. Click on image to expand.

What follows is a brief description of the “actin-related protein 2/3 complex” (Arp2/3) in its biological context. References are provided in the form of hyperlinks to abstracts in PubMed (see end of section).

The actin-related protein 2/3 complex (Arp 2/3) belongs to the family of actin-related proteins which have a diverse range of cellular functions (1). Arp2/3 is a heteroheptameric protein which was first purified from Acanthamoeba using affinity chromotography (2). Arp 2/3 is a 220kDa complex for which numerous homologues of each subunit have been found to exist across a range of diverse eukaryotes, indicating a conserved structure and function (3).

This protein complex has an important function in initiating actin polymerisation in the cell cytoskeleton. Arp 2/3 binds directly to actin filaments and facilitates the elongation of actin protofilaments from the barbed end, through the nucleation and cross linking of successive filaments of F actin (4). The polymerisation of actin has numerous roles which include the cell front protrusion of the lamellipodium during the migration of simple unicellular organisms such as amoeba, and bacteria such as Listeria can develop an ‘actin tail’ to facilitate intracellular movement during infection (5). Recent investigation into Arp2/3 silencing using siRNA led to a reduction in cell migration in all the Pancreatic cancer cell lines studied, consistent with the proposed role of Arp2/3 in cell movement (6).

Seven subunits constitute the Arp 2/3 complex in humans: two actin-related proteins (i.e. Arp2 and Arp3) and 5 additional subunits p41-Arc (ARPC1B), p34-Arc (ARPC2), p21-Arc (ARPC3), p20-Arc (ARPC4) and p16-Arc (ARPC5). Several different isoforms have been identified and characterised for each subunit in the Homo sapiens species (4).

The p20 and p34 subunits form a heterodimer in the central core which is surrounded by the 5 other subunits. The p41 subunit consists of a beta propeller structure with seven WD repeats. The core central p34/p20 heterodimer has N terminal alpha/beta domains which interact via C-terminal alpha helices, whilst the p16 and p21 subunits consist of a globular alpha helical structure. The actin-related proteins 2 and 3 share folds similar to actin (7).

The respective functions of each subunit have been probed through deleting various combinations of subunit and comparing the resulting nucleation activity to the wild type. Consequently, the Arp3 subunit has been shown to be crucial for nucleation of actin filaments, whilst the p41, p21 and p16 are not a requirement but do contribute to the efficiency of the nucleation process. Furthermore, Arp2 has been recognised as the ATP binding site, whilst the p34 -p20 dimer has been shown to play a role in binding and cross linking F actin filaments (4).

The Arp 2/3 is activated through two main groups of nucleation promoting factors, WASP and Scar/WAVE, which act by inducing conformational changes in the complex and delivering the initial actin monomer to the filament. WASP activated Arp2/3 actin polymerisation plays a role in membrane trafficking, whereas activation through the Scar/WAVE pathway plays a role in cell front protrusion during cell migration.  These two different promoting factors are therefore stimulated through different pathways, and consequently activate actin polymerisation of different downstream targets (8).