Disease relevance of ACTR3

• Both adherens-like junctions and TJs were enriched in actin-related protein 3 and neuronal Wiskott-Aldrich syndrome protein (N-WASP), and their assembly was prevented by the N-WASP inhibitor wiskostatin [1].
• Since actin-related protein (Arp) 2/3 complex acts as a nucleus for actin polymerization, in this study, we immunohistochemically investigated the expression of Arp2 and Arp3 in 175 colorectal tumors in various stages of neoplastic progression [2].
• The frequency of expression of Arp2 and Arp3 (Arp2 and 3) by the stromal cells increased with the atypia of the colorectal neoplasms, from 5.5% (3/55) in adenoma with mild or moderate atypia, to 11.8% (2/17) in adenoma with severe atypia, 53.3% (16/30) in intramucosal carcinoma, and 91.8% (67/73) in invasive carcinoma (P<0.0001) [2].

High impact information on ACTR3

• We predict that WASp/Scar proteins activate Arp2/3 complex by bringing Arp2 into proximity with Arp3 for nucleation of a branch on the side of a preexisting actin filament [3].
• ATP hydrolysis by Arp2, and possibly Arp3, is essential for efficient y-branch dissociation in vitro [4].
• Our data suggest a bivalent attachment of WASp to Arp3 (within peptides 162-191 and 318-329) and Arp2 (within peptides 66-80 and 87-97) [5].
• The Arp2/3 complex, a seven-subunit protein complex containing two actin-related proteins, Arp2 and Arp3, initiates formation of actin filament networks in response to intracellular signals [6].
• Binding of N-WASP WA increases the affinity of both Arp2 and Arp3 for ATP but does not alter the stoichiometry of nucleotides bound in the presence of saturating concentrations of ATP [6].

Biological context of ACTR3

• A tccP mutant did not affect Tir translocation and focusing but failed to recruit alpha-actinin, Arp3, N-WASP and actin to the site of bacterial adhesion [7].
• Sequence analysis revealed that this novel gene has an open reading frame of 210 amino acid residues showing 89% amino acid identity with human Arp3, which is one of the actin-related proteins [8].
• Partial amino acid sequences of the peptides derived from the 45K and 40K proteins showed that these proteins are homologous to Arp3 and Arp2 subfamilies of actin-related proteins, respectively [9].
• Consistent with a common binding site on Arp3, a saturating concentration of VCA abolished binding of cortactin to Arp2/3 complex [10].
• Surprisingly, Arp3 organized into similar adhesion contacts in cells expressing wild-type beta(3) but not in those expressing a nonphosphorylatable mutant of beta(3), suggesting that beta(3) phosphorylation is required for sequestration of Arp3 to adhesion complexes [11].

Anatomical context of ACTR3

• The Arp2/3 complex, a stable assembly of two actin-related proteins (Arp2 and Arp3) with five other subunits, caps the pointed end of actin filaments and nucleates actin polymerization with low efficiency [12].
• BACKGROUND: The actin-related proteins Arp2 and Arp3 are part of a seven-protein complex which is localized in the lamellipodia of a variety of cell types, and in actin-rich spots of unknown function [13].
• Arp2 and Arp3 showed identical expression patterns, and both were expressed in the stromal cells around neoplastic tubules or glands and in the tumor cells themselves [2].
• Suppression of actin stress fiber formation by an inhibitor to Rho kinase disrupted Arp3 organization while prolonging beta(3) phosphorylation throughout the adhesion time course [11].
• Beta 3 integrin phosphorylation is essential for Arp3 organization into leukocyte alpha V beta 3-vitronectin adhesion contacts [11].

Associations of ACTR3 with chemical compounds

• We show here that adenosine nucleotides bind with micromolar affinity to both Arp2 and Arp3 and that hydrolyzable ATP is required for actin nucleation activity [6].

Physical interactions of ACTR3

• We propose that ActA and endogenous WASP family proteins promote Arp2/3-dependent nucleation by similar mechanisms and require simultaneous binding of Arp2 and Arp3 [14].

Other interactions of ACTR3

• CLANs lacked Arp3 and cortactin [15].

Analytical, diagnostic and therapeutic context of ACTR3

• MATERIALS AND METHODS: Western blot analysis was used to determine levels of Arp2 and Arp3, two components of the Arp2/3 complex in osteoclast-like cells [16].
• In addition, ectopically expressed full-length GFP-N-WASP was recruited by S. flexneri but not R. rickettsii, and Arp3 was detected by indirect immunofluorescence in S. flexneri actin tails but not within R. rickettsii actin tails [17].
• Most Arp3 protein is found in a multi-protein complex; we purified this complex and determined the sequences of each of the protein subunits using a high-accuracy mass peptide-mapping technique [18].
• Confocal microscopy showed Arp3 accumulation in AGS cells infected with wild-type H. pylori, but not in response to infection with the cagE mutant [19].

References