Alternative titles; symbols
HGNC Approved Gene Symbol: ACTR3
Cytogenetic location: 2q14.1 Genomic coordinates (GRCh38) : 2:113,889,934-113,962,596 (from NCBI)
The Arp2/3 protein complex has been implicated in the control of actin polymerization in cells. The human complex consists of 7 subunits: the actin-related proteins ARP2 (ACTR2; 604221) and ARP3 (ACTR3), ARC41 (ARPC1B; 604223), ARC34 (ARPC2; 604224), ARC21 (ARPC3; 604225), ARC20 (ARPC4; 604226), and ARC16 (ARPC5; 604227). See ACTR2 for additional information about the Arp2/3 complex.
By searching an EST database with peptide sequences from the 7 subunits of the human ARP2/3 complex, Welch et al. (1997) identified full-length human cDNAs encoding each subunit. The ARP3 cDNA encodes a deduced 418-amino acid protein that is identical to bovine Arp3, 59% identical to S. pombe Arp3, and 58% identical to S. cerevisiae Arp3. ARP3 localizes to the lamellipodia of stationary and locomoting fibroblasts. It also localizes to the actin tails assembled by moving intracellular Listeria monocytogenes bacteria and to actin clouds surrounding stationary L. monocytogenes (Welch et al., 1997). ARP3 was not detected in cellular bundles of actin filaments.
Machesky et al. (1997) purified the ARP2/3 complex from human neutrophils and sequenced peptides from each of the subunits. Western blot analysis detected ARP3 and ARC34 in all human tissues tested.
In a functional genomic screen using RNA interference to identify human genes involved in ciliogenesis control, Kim et al. (2010) identified 2 gelsolin family proteins, GSN (137350) and AVIL (613397), which regulate cytoskeletal actin organization by severing actin filaments. Depletion of GSN proteins by 2 independent siRNAs significantly reduced ciliated cell numbers, indicating that actin filament severing is involved in ciliogenesis. In contrast, silencing of actin-related protein ACTR3, which is a major constituent of the ARP2/3 complex that is necessary for nucleating actin polymerization at filament branches, caused a significant increase in cilium length and also facilitated ciliogenesis independently of serum starvation. Kim et al. (2010) concluded that their observations indicated an inhibitory role of branched actin network formation in ciliogenesis.
Volkmann et al. (2001) performed electron cryomicroscopy and 3-dimensional reconstruction of Acanthamoeba castellanii and S. cerevisiae Arp2/3 complexes bound to the WASP (301000) carboxy-terminal domain. Asymmetric, oblate ellipsoids were revealed. Image analysis of actin branches indicated that the complex binds the side of the mother filament, and ARP2 and ARP3 are the first 2 subunits of the daughter filament. Comparison to the actin-free WASP-activated complexes suggests that branch initiation involves large-scale structural rearrangements within ARP2/3.
Robinson et al. (2001) determined the crystal structure of bovine ARP2/3 complex at 2.0-angstrom resolution. ARP2 and ARP3 are folded like actin, with distinctive surface features. Subunits ARPC2 and ARPC4 in the core of the complex associate through long carboxy-terminal alpha helices and have similarly folded amino-terminal alpha/beta domains. ARPC1 is a 7-blade beta propeller with an insertion that may associate with the side of an actin filament. ARPC3 and ARPC5 are globular alpha-helical subunits. Robinson et al. (2001) predicted 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.
Kim, J., Lee, J. E., Heynen-Genel, S., Suyama, E., Ono, K., Lee, K., Ideker, T., Aza-Blanc, P., Gleeson, J. G. Functional genomic screen for modulators of ciliogenesis and cilium length. Nature 464: 1048-1051, 2010. [PubMed: 20393563] [Full Text: https://doi.org/10.1038/nature08895]
Machesky, L. M., Reeves, E., Wientjes, F., Mattheyse, F. J., Grogan, A., Totty, N. F., Burlingame, A. L., Hsuan, J. J., Segal, A. W. Mammalian actin-related protein 2/3 complex localizes to regions of lamellipodial protrusion and is composed of evolutionarily conserved proteins. Biochem. J. 328: 105-112, 1997. [PubMed: 9359840] [Full Text: https://doi.org/10.1042/bj3280105]
Robinson, R. C., Turbedsky, K., Kaiser, D. A., Marchand, J.-B., Higgs, H. N., Choe, S., Pollard, T. D. Crystal structure of Arp2/3 complex. Science 294: 1679-1684, 2001. [PubMed: 11721045] [Full Text: https://doi.org/10.1126/science.1066333]
Volkmann, N., Amann, K. J., Stoilova-McPhie, S., Egile, C., Winter, D. C., Hazelwood, L., Heuser, J. E., Li, R., Pollard, T. D., Hanein, D. Structure of Arp2/3 complex in its activated state and in actin filament branch junctions. Science 293: 2456-2459, 2001. [PubMed: 11533442] [Full Text: https://doi.org/10.1126/science.1063025]
Welch, M. D., DePace, A. H., Verma, S., Iwamatsu, A., Mitchison, T. J. The human Arp2/3 complex is composed of evolutionarily conserved subunits and is localized to cellular regions of dynamic actin filament assembly. J. Cell Biol. 138: 375-384, 1997. [PubMed: 9230079] [Full Text: https://doi.org/10.1083/jcb.138.2.375]
Welch, M. D., Iwamatsu, A., Mitchison, T. J. Actin polymerization is induced by Arp2/3 protein complex at the surface of Listeria monocytogenes. Nature 385: 265-269, 1997. [PubMed: 9000076] [Full Text: https://doi.org/10.1038/385265a0]