actin related protein 2 3 complex


Summary: A complex of seven proteins including ARP2 PROTEIN and ARP3 PROTEIN that plays an essential role in maintenance and assembly of the CYTOSKELETON. Arp2-3 complex binds WASP PROTEIN and existing ACTIN FILAMENTS, and it nucleates the formation of new branch point filaments.

Top Publications

  1. Akin O, Mullins R. Capping protein increases the rate of actin-based motility by promoting filament nucleation by the Arp2/3 complex. Cell. 2008;133:841-51 pubmed publisher
    ..By reorganizing their architecture, dendritic actin networks harness the same assembly kinetics to drive different rates of motility. ..
  2. DesMarais V, Yamaguchi H, Oser M, Soon L, Mouneimne G, Sarmiento C, et al. N-WASP and cortactin are involved in invadopodium-dependent chemotaxis to EGF in breast tumor cells. Cell Motil Cytoskeleton. 2009;66:303-16 pubmed publisher
  3. Kong L, Sun L, Zhang H, Liu Q, Liu Y, Qin L, et al. An essential role for RIG-I in toll-like receptor-stimulated phagocytosis. Cell Host Microbe. 2009;6:150-61 pubmed publisher
    ..Thus, the regulatory functions of RIG-I are strikingly broad, including a role not only in antiviral responses but in antibacterial responses as well. ..
  4. Lai F, Szczodrak M, Oelkers J, Ladwein M, Acconcia F, Benesch S, et al. Cortactin promotes migration and platelet-derived growth factor-induced actin reorganization by signaling to Rho-GTPases. Mol Biol Cell. 2009;20:3209-23 pubmed publisher
    ..Furthermore, we propose that cortactin promotes cell migration indirectly, through contributing to activation of selected Rho-GTPases. ..
  5. Rajmohan R, Wong M, Meng L, Munn A, Thanabalu T. Las17p-Vrp1p but not Las17p-Arp2/3 interaction is important for actin patch polarization in yeast. Biochim Biophys Acta. 2009;1793:825-35 pubmed publisher
    ..Using these mutant and truncated forms of yeast WASP we provide novel evidence that WASP interaction with WIP is more important than interaction with Arp2/3 for polarized actin assembly and endocytosis in yeast. ..
  6. Nolen B, Tomasevic N, Russell A, Pierce D, Jia Z, McCormick C, et al. Characterization of two classes of small molecule inhibitors of Arp2/3 complex. Nature. 2009;460:1031-4 pubmed publisher
    ..Two inhibitors with different mechanisms of action provide a powerful approach for studying the Arp2/3 complex in living cells. ..
  7. Dharmalingam E, Haeckel A, Pinyol R, Schwintzer L, Koch D, Kessels M, et al. F-BAR proteins of the syndapin family shape the plasma membrane and are crucial for neuromorphogenesis. J Neurosci. 2009;29:13315-27 pubmed publisher
    ..Our data thus reveal that syndapin I is crucial for neuromorphogenesis and that different N-WASP activators ensure fine control of N-WASP activity and have distinct functions during neuronal network formation. ..
  8. Chan C, Beltzner C, Pollard T. Cofilin dissociates Arp2/3 complex and branches from actin filaments. Curr Biol. 2009;19:537-45 pubmed publisher
    ..Cofilin rapidly dissociates Arp2/3 complex and branches by direct competition for binding sites on the actin filament and by propagation of structural changes in the actin filament that reduce affinity for Arp2/3 complex. ..
  9. Benjamin J, Kwiatkowski A, Yang C, Korobova F, Pokutta S, Svitkina T, et al. AlphaE-catenin regulates actin dynamics independently of cadherin-mediated cell-cell adhesion. J Cell Biol. 2010;189:339-52 pubmed publisher
    ..In contrast, sequestration of cytosolic alphaE-catenin to the plasma membrane reduces membrane dynamics. These results demonstrate that the cytosolic pool of alphaE-catenin regulates actin dynamics independently of cell-cell adhesion. ..

More Information


  1. Hu L, Papoian G. Mechano-chemical feedbacks regulate actin mesh growth in lamellipodial protrusions. Biophys J. 2010;98:1375-84 pubmed publisher
    ..Overall, our work emphasizes that elongation and nucleation processes work highly cooperatively in determining the optimal protrusion speed for the actin mesh in lamellipodia. ..
  2. Padrick S, Rosen M. Physical mechanisms of signal integration by WASP family proteins. Annu Rev Biochem. 2010;79:707-35 pubmed publisher
    ..These regulatory principles, derived from studies of WASP and N-WASP, are likely to apply broadly across the family...
  3. Weisswange I, Newsome T, Schleich S, Way M. The rate of N-WASP exchange limits the extent of ARP2/3-complex-dependent actin-based motility. Nature. 2009;458:87-91 pubmed publisher
    ..We suggest that the exchange rate of N-WASP controls the rate of ARP2/3-complex-dependent actin-based motility by regulating the extent of actin polymerization by antagonizing filament capping. ..
  4. Bretschneider T, Anderson K, Ecke M, Müller Taubenberger A, Schroth Diez B, Ishikawa Ankerhold H, et al. The three-dimensional dynamics of actin waves, a model of cytoskeletal self-organization. Biophys J. 2009;96:2888-900 pubmed publisher
    ..These data show that force-generating, highly organized supramolecular networks are autonomously formed in live cells from molecular motors and proteins controlling actin polymerization and depolymerization. ..
  5. Molli P, Li D, Bagheri Yarmand R, Pakala S, Katayama H, Sen S, et al. Arpc1b, a centrosomal protein, is both an activator and substrate of Aurora A. J Cell Biol. 2010;190:101-14 pubmed publisher
    ..Together, these findings reveal a new function for Arpc1b in centrosomal homeostasis. Arpc1b is both a physiological activator and substrate of Aurora A kinase and these interactions help to maintain mitotic integrity in mammalian cells...
  6. Oser M, Yamaguchi H, Mader C, Bravo Cordero J, Arias M, Chen X, et al. Cortactin regulates cofilin and N-WASp activities to control the stages of invadopodium assembly and maturation. J Cell Biol. 2009;186:571-87 pubmed publisher
  7. D Ambrosio M, Vale R. A whole genome RNAi screen of Drosophila S2 cell spreading performed using automated computational image analysis. J Cell Biol. 2010;191:471-8 pubmed publisher
  8. Kelly A, Kranitz H, Dötsch V, Mullins R. Actin binding to the central domain of WASP/Scar proteins plays a critical role in the activation of the Arp2/3 complex. J Biol Chem. 2006;281:10589-97 pubmed
  9. To C, Shilton B, Di Guglielmo G. Synthetic triterpenoids target the Arp2/3 complex and inhibit branched actin polymerization. J Biol Chem. 2010;285:27944-57 pubmed publisher
    ..Taken together, our data suggest that synthetic triterpenoids target Arp3 and branched actin polymerization to inhibit cell migration. ..
  10. Monfregola J, Napolitano G, D Urso M, Lappalainen P, Ursini M. Functional characterization of Wiskott-Aldrich syndrome protein and scar homolog (WASH), a bi-modular nucleation-promoting factor able to interact with biogenesis of lysosome-related organelle subunit 2 (BLOS2) and gamma-tubulin. J Biol Chem. 2010;285:16951-7 pubmed publisher
    ..Moreover, our data suggest that WASH is also a component of the BLOC-1 complex that is associated with the centrosomes. ..
  11. Kraikivski P, Slepchenko B. Quantifying a pathway: kinetic analysis of actin dendritic nucleation. Biophys J. 2010;99:708-15 pubmed publisher
    ..The idea is tested by simulating the proposed experiments with the use of spatial stochastic modeling. ..
  12. Achard V, Martiel J, Michelot A, Guerin C, Reymann A, Blanchoin L, et al. A "primer"-based mechanism underlies branched actin filament network formation and motility. Curr Biol. 2010;20:423-8 pubmed publisher
  13. Derivery E, Gautreau A. Generation of branched actin networks: assembly and regulation of the N-WASP and WAVE molecular machines. Bioessays. 2010;32:119-31 pubmed publisher
    ..Moreover, this review attempts to put together diverse observations concerning the WAVE complex in the conceptual frame of an in vivo assembly pathway that has gained support from the recent identification of a precursor. ..
  14. Boettner D, D Agostino J, Torres O, Daugherty Clarke K, Uygur A, Reider A, et al. The F-BAR protein Syp1 negatively regulates WASp-Arp2/3 complex activity during endocytic patch formation. Curr Biol. 2009;19:1979-87 pubmed publisher
    ..Together, these data identify Syp1 as a novel negative regulator of WASp-Arp2/3 complex that helps choreograph the precise timing of actin assembly during endocytosis. ..
  15. Rottner K, Hänisch J, Campellone K. WASH, WHAMM and JMY: regulation of Arp2/3 complex and beyond. Trends Cell Biol. 2010;20:650-61 pubmed publisher
    ..Uncovering the physiological relevance of these unique activities will require concerted efforts from multiple disciplines, and is sure to impact our understanding of how the cytoskeleton controls so many dynamic subcellular events. ..
  16. Loomis P, Kelly A, Zheng L, Changyaleket B, Sekerkova G, Mugnaini E, et al. Targeted wild-type and jerker espins reveal a novel, WH2-domain-dependent way to make actin bundles in cells. J Cell Sci. 2006;119:1655-65 pubmed
    ..Espins do not activate the Arp2/3 complex in vitro, and bundle assembly is not indicative of in-vitro nucleation activity. Our results suggest a novel way to build actin bundles at specific sites in cells. ..
  17. Ditlev J, Vacanti N, Novak I, Loew L. An open model of actin dendritic nucleation. Biophys J. 2009;96:3529-42 pubmed publisher, it can be accessed, analyzed, modified, and extended. ..
  18. Mitsushima M, Aoki K, Ebisuya M, Matsumura S, Yamamoto T, Matsuda M, et al. Revolving movement of a dynamic cluster of actin filaments during mitosis. J Cell Biol. 2010;191:453-62 pubmed publisher
    ..These results identify Arp2/3 complex as a key factor in the generation of the dynamic actin cluster during mitosis. ..
  19. Gildor B, Massarwa R, Shilo B, Schejter E. Making muscles: Arp, two, three. Fly (Austin). 2010;4:145-8 pubmed
    ..Our approach also allows us to assess the involvement of the Arp2/3 machinery in formation of a distinct, fusion-associated actin structure. ..
  20. Heinrich D, Youssef S, Schroth Diez B, Engel U, Aydin D, Blümmel J, et al. Actin-cytoskeleton dynamics in non-monotonic cell spreading. Cell Adh Migr. 2008;2:58-68 pubmed
    ..We conclude that non-monotonic cell spreading is characterized by spatiotemporal patterns formed by motor proteins together with regulatory proteins that either promote or terminate actin polymerization on the scale of seconds. ..
  21. Chong R, Swiss R, Briones G, Stone K, Gulcicek E, Agaisse H. Regulatory mimicry in Listeria monocytogenes actin-based motility. Cell Host Microbe. 2009;6:268-78 pubmed publisher
    ..Comparisons based on ActA amino acid sequence suggest that unrelated pathogens that display actin-based motility may have evolved a similar strategy of regulatory mimicry. ..
  22. Ramesh N, Geha R. Recent advances in the biology of WASP and WIP. Immunol Res. 2009;44:99-111 pubmed publisher
    ..In this review, we have summarized recent developments in the biology of WASP and the role of WIP in regulating WASP function. We also discuss WASP-independent functions of WIP. ..
  23. Soderling S. Grab your partner with both hands: cytoskeletal remodeling by Arp2/3 signaling. Sci Signal. 2009;2:pe5 pubmed publisher
    ..Emerging data on an important regulator of actin dynamics, the actin-related protein 2 and 3 (Arp2/3) complex, suggest a model of how this may occur. ..
  24. Zhang Z, Pfaendtner J, Grafmüller A, Voth G. Defining coarse-grained representations of large biomolecules and biomolecular complexes from elastic network models. Biophys J. 2009;97:2327-37 pubmed publisher
  25. Anitei M, Stange C, Parshina I, Baust T, Schenck A, Raposo G, et al. Protein complexes containing CYFIP/Sra/PIR121 coordinate Arf1 and Rac1 signalling during clathrin-AP-1-coated carrier biogenesis at the TGN. Nat Cell Biol. 2010;12:330-40 pubmed publisher
  26. Saedler R, Jakoby M, Marin B, Galiana Jaime E, Hulskamp M. The cell morphogenesis gene SPIRRIG in Arabidopsis encodes a WD/BEACH domain protein. Plant J. 2009;59:612-21 pubmed publisher
    ..This complete phenotypic overlap suggests that this WD40/BEACH domain protein and the actin-regulating ARP2/3 pathway are involved in similar growth processes. ..
  27. Butler B, Cooper J. Distinct roles for the actin nucleators Arp2/3 and hDia1 during NK-mediated cytotoxicity. Curr Biol. 2009;19:1886-96 pubmed publisher
    ..These studies reveal novel distinctions and relationships among the functions of Arp2/3, formins, and microtubules in cells. Notably, a formin mediates the capture of microtubules at the cell periphery. ..
  28. Mellor H. The role of formins in filopodia formation. Biochim Biophys Acta. 2010;1803:191-200 pubmed publisher
  29. Yoshikawa Y, Ogawa M, Hain T, Yoshida M, Fukumatsu M, Kim M, et al. Listeria monocytogenes ActA-mediated escape from autophagic recognition. Nat Cell Biol. 2009;11:1233-40 pubmed publisher
    ..Our findings indicate that ActA-mediated host protein recruitment is a unique bacterial disguise tactic to escape from autophagy. ..
  30. Hänisch J, Ehinger J, Ladwein M, Rohde M, Derivery E, Bosse T, et al. Molecular dissection of Salmonella-induced membrane ruffling versus invasion. Cell Microbiol. 2010;12:84-98 pubmed publisher
  31. Lee K, Gallop J, Rambani K, Kirschner M. Self-assembly of filopodia-like structures on supported lipid bilayers. Science. 2010;329:1341-5 pubmed publisher
    ..We propose that filopodia form via clustering of Arp2/3 complex activators, self-assembly of filopodial tip complexes on the membrane, and outgrowth of actin bundles...
  32. Ungar L, Yosef N, Sela Y, Sharan R, Ruppin E, Kupiec M. A genome-wide screen for essential yeast genes that affect telomere length maintenance. Nucleic Acids Res. 2009;37:3840-9 pubmed publisher
    ..The newly identified genes span a variety of cellular processes, including protein degradation, pre-mRNA splicing and DNA replication. ..
  33. Nakano K, Kuwayama H, Kawasaki M, Numata O, Takaine M. GMF is an evolutionarily developed Adf/cofilin-super family protein involved in the Arp2/3 complex-mediated organization of the actin cytoskeleton. Cytoskeleton (Hoboken). 2010;67:373-82 pubmed publisher
    ..Given the functional plasticity of ADF-H, GMF-family proteins possibly have changed their target from conventional actin to Arps through molecular evolution. ..
  34. Gunst S, Zhang W. Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction. Am J Physiol Cell Physiol. 2008;295:C576-87 pubmed publisher
    ..Better understanding of the physiological function of these dynamic cytoskeletal processes in smooth muscle may provide important insights into the physiological regulation of smooth muscle tissues...
  35. Zencheck W, Xiao H, Nolen B, Angeletti R, Pollard T, Almo S. Nucleotide- and activator-dependent structural and dynamic changes of arp2/3 complex monitored by hydrogen/deuterium exchange and mass spectrometry. J Mol Biol. 2009;390:414-27 pubmed publisher
  36. Peterson J, Lebensohn A, Pelish H, Kirschner M. Biochemical suppression of small-molecule inhibitors: a strategy to identify inhibitor targets and signaling pathway components. Chem Biol. 2006;13:443-52 pubmed
    ..This work introduces a general method for using low-micromolar chemical inhibitors to identify both inhibitor targets and other components of a signaling pathway. ..
  37. Liu R, Abreu Blanco M, Barry K, Linardopoulou E, Osborn G, Parkhurst S. Wash functions downstream of Rho and links linear and branched actin nucleation factors. Development. 2009;136:2849-60 pubmed publisher
    ..Our results establish Wash and Rho as regulators of both linear- and branched-actin networks, and suggest an Arp2/3-mediated mechanism for how cells might coordinately regulate these structures. ..
  38. Dayel M, Akin O, Landeryou M, Risca V, Mogilner A, Mullins R. In silico reconstitution of actin-based symmetry breaking and motility. PLoS Biol. 2009;7:e1000201 pubmed publisher
    ..The fact that the model not only mirrors our in vitro observations, but also makes novel predictions that we confirm by experiment, suggests that the model captures much of the essence of actin-based motility in this system. ..
  39. Kotchoni S, Zakharova T, Mallery E, Le J, El Assal S, Szymanski D. The association of the Arabidopsis actin-related protein2/3 complex with cell membranes is linked to its assembly status but not its activation. Plant Physiol. 2009;151:2095-109 pubmed publisher
    ..Membrane binding is linked to complex assembly status and not to the extent to which it is activated. Mutant analyses implicate ARP2 as an important subunit for membrane association. ..
  40. Kang H, Carlsson A, Tang J. Kinetic overshoot in actin network assembly induced jointly by branching and capping proteins. Phys Rev E Stat Nonlin Soft Matter Phys. 2009;80:041913 pubmed
    ..These results establish a natural link between the kinetic theory of actin assembly in vitro and the cytoskeletal structure and actin dynamics in motile cells. ..
  41. Liu J, Yue P, Artym V, Mueller S, Guo W. The role of the exocyst in matrix metalloproteinase secretion and actin dynamics during tumor cell invadopodia formation. Mol Biol Cell. 2009;20:3763-71 pubmed publisher
    ..Together, our results suggest that the exocyst plays important roles in cell invasion by mediating the secretion of MMPs at focal degrading sites and regulating Arp2/3-mediated actin dynamics. ..
  42. Hotulainen P, Llano O, Smirnov S, Tanhuanpää K, Faix J, Rivera C, et al. Defining mechanisms of actin polymerization and depolymerization during dendritic spine morphogenesis. J Cell Biol. 2009;185:323-39 pubmed publisher
    ..Finally, we show that perturbation of these key steps in actin dynamics results in altered synaptic transmission. ..
  43. Henson J, Cheung D, Fried C, Shuster C, McClellan M, Voss M, et al. Structure and dynamics of an Arp2/3 complex-independent component of the lamellipodial actin network. Cell Motil Cytoskeleton. 2009;66:679-92 pubmed publisher
  44. Ren G, Crampton M, Yap A. Cortactin: Coordinating adhesion and the actin cytoskeleton at cellular protrusions. Cell Motil Cytoskeleton. 2009;66:865-73 pubmed publisher
    ..We further argue that regulatory proteins, such as cortactin, serve to coordinate the molecular components of this protrusive apparatus into a cohesive module. ..
  45. Derivery E, Lombard B, Loew D, Gautreau A. The Wave complex is intrinsically inactive. Cell Motil Cytoskeleton. 2009;66:777-90 pubmed publisher
    ..Importantly, the approach we describe here for multiprotein complex purification is likely applicable to a wide range of human multiprotein complexes. ..
  46. Gandhi M, Smith B, Bovellan M, Paavilainen V, Daugherty Clarke K, Gelles J, et al. GMF is a cofilin homolog that binds Arp2/3 complex to stimulate filament debranching and inhibit actin nucleation. Curr Biol. 2010;20:861-7 pubmed publisher
  47. Campellone K, Welch M. A nucleator arms race: cellular control of actin assembly. Nat Rev Mol Cell Biol. 2010;11:237-51 pubmed publisher
    ..Formin nucleators with additional biochemical and cellular activities have also been uncovered. Finally, the Spire, cordon-bleu and leiomodin nucleators have revealed new ways of overcoming the kinetic barriers to actin polymerization. ..
  48. Blanchoin L, Boujemaa Paterski R. Inhibitors target actin nucleators. Chem Biol. 2009;16:1125-6 pubmed publisher
    ..2009) and formins (Gauvin et al., 2009), these small molecules provide useful laboratory tools to dissect the link between actin nucleators and actin-based structures in living cells. ..
  49. Madhavan R, Gong Z, Ma J, Chan A, Peng H. The function of cortactin in the clustering of acetylcholine receptors at the vertebrate neuromuscular junction. PLoS ONE. 2009;4:e8478 pubmed publisher
    ..Our results suggest a novel function of phosphorylation-dependent cortactin signaling downstream from agrin/MuSK in facilitating AChR clustering at the developing NMJ. ..
  50. Grötsch H, Giblin J, Idrissi F, Fernández Golbano I, Collette J, Newpher T, et al. Calmodulin dissociation regulates Myo5 recruitment and function at endocytic sites. EMBO J. 2010;29:2899-914 pubmed publisher
    ..Concomitantly, calmodulin dissociation triggered Myo5 binding to Vrp1, extended the myosin-I lifespan at endocytic sites and activated Myo5-induced actin polymerization. ..
  51. Lee K, Liu A. Force-velocity relation for actin-polymerization-driven motility from Brownian dynamics simulations. Biophys J. 2009;97:1295-304 pubmed publisher
    ..The behavior is consistent with experiments and with our recently proposed self-diffusiophoretic mechanism for actin-polymerization-driven motility. New in vitro experiments to measure the force-velocity relation are proposed. ..
  52. Epp E, Walther A, Lépine G, Leon Z, Mullick A, Raymond M, et al. Forward genetics in Candida albicans that reveals the Arp2/3 complex is required for hyphal formation, but not endocytosis. Mol Microbiol. 2010;75:1182-98 pubmed publisher
    ..albicans showed that uptake of membrane components from the plasma membrane to vacuolar structures is not dependent on this actin nucleating machinery. ..
  53. Ahuja R, Pinyol R, Reichenbach N, Custer L, Klingensmith J, Kessels M, et al. Cordon-bleu is an actin nucleation factor and controls neuronal morphology. Cell. 2007;131:337-50 pubmed
    ..Correspondingly, Cobl depletion results in decreased dendritic arborization. Thus, Cobl is an actin nucleator controlling neuronal morphology and development. ..