Arp2/3 complex

Image:Arp23 side branching model.png

Image:Arp23 barbed end branching model.png

Many actin-related molecules create a free barbed end for polymerization by uncapping or severing pre-existing filaments and using these as actin nucleation cores. However, the Arp2/3 complex stimulates actin polymerization by creating a new nucleation core. Actin nucleation is an initial step in the formation of an actin filament. The nucleation core activity of Arp2/3 is activated by Nucleation Promoting Factors (NPFs) including members of the Wiskott-Aldrich syndrome family protein (WASP, N-WASP, WAVE, and WASH proteins). The V domain of a WASP protein interacts with actin monomers while the CA region associates with the Arp2/3 complex to create a nucleation core. However, de novo nucleation followed by polymerization is not sufficient to form integrated actin networks, since these newly synthesized polymers would not be associated with pre-existing filaments. Thus, the Arp2/3 complex binds to pre-existing filaments so that the new filaments can grow on the old ones and form a functional actin cytoskeleton. Capping proteins limit actin polymerization to the region activated by the Arp2/3 complex, and the elongated filament ends are recapped to prevent depolymerization and thus conserve the actin filament.

The Arp2/3 complex simultaneously controls nucleation of actin polymerization and branching of filaments. Moreover, autocatalysis is observed during Arp2/3-mediated actin polymerization. In this process, the newly formed filaments activate other Arp2/3 complexes, facilitating the formation of branched filaments.

The mechanism of actin filament initiation by Arp2/3 has been disputed. The question is where the complex binds the filament and nucleates a "daughter" filament. Historically two models have been proposed. Recent results favour the side branching model, in which the Arp2/3 complex binds to the side of a pre-existing ("mother") filament at a point different from the nucleation site. Although the field lacks a high-resolution crystal structure, data from electron microscopy, together with biochemical data on the [http://www.dayel.com/research/arp23-complex/ filament nucleation and capping mechanisms of the Arp2/3 complex], favour side branching. In the alternative barbed end branching model, Arp2/3 only associates at the barbed end of growing filaments, allowing for the elongation of the original filament and the formation of a branched filament., a model based on kinetic analysis and optical microscopy.

Recent computer docking, independently confirmed by EM data, favors a side-branching model. ARPC2 and ARPC4 together form an area that attach the base of the branch to the side of a mother filament.{{cite journal |last1=Goley |first1=ED |last2=Rammohan |first2=A |last3=Znameroski |first3=EA |last4=Firat-Karalar |first4=EN |last5=Sept |first5=D |last6=Welch |first6=MD |title=An actin-filament-binding interface on the Arp2/3 complex is critical for nucleation and branch stability. |journal=Proceedings of the National Academy of Sciences of the United States of America |date=4 May 2010 |volume=107 |issue=18 |pages=8159–64 |doi=10.1073/pnas.0911668107 |pmid=20404198 |pmc=2889539|bibcode=2010PNAS..107.8159G |doi-access=free }} Large conformational changes occur on nucleotide and WASP binding.{{cite journal |last1=Padrick |first1=S. B. |last2=Doolittle |first2=L. K. |last3=Brautigam |first3=C. A. |last4=King |first4=D. S. |last5=Rosen |first5=M. K. |title=Arp2/3 complex is bound and activated by two WASP proteins |journal=Proceedings of the National Academy of Sciences |date=16 August 2011 |volume=108 |issue=33 |pages=E472–E479 |doi=10.1073/pnas.1100236108 |pmid=21676863 |language=en |issn=0027-8424|pmc=3158169 |doi-access=free }}

The Arp2/3 complex appears to be important in a variety of specialized cell functions that involve the actin cytoskeleton.

The complex is found in cellular regions characterized by dynamic actin filament activity: in macropinocytic cups, in the leading edge of motile cells (lamellipodia), and in motile actin patches in yeast. In mammals and the social amoeba Dictyostelium discoideum it is required for phagocytosis. The complex has also been shown to be involved in the establishment of cell polarity and the migration of fibroblast monolayers in a wound-healing model. In mammalian oocytes, the Arp2/3 complex is involved in oocyte asymmetric division and polar body emission, which result from the failure of spindle migration (a unique feature of oocyte division) and cytokinesis. Moreover, enteropathogenic organisms like Listeria monocytogenes and Shigella use the Arp2/3 complex for actin-polymerization- dependent rocketing movements. The Arp2/3 complex also regulates the intracellular motility of endosomes, lysosomes, pinocytic vesicles, and mitochondria. Moreover, recent studies show that the Arp2/3 complex is essential for proper polar cell expansion in plants. Arp2/3 mutations in Arabidopsis thaliana result in abnormal filament organization, which in turn affects the expansion of trichomes, pavement cells, hypocotyl cells, and root hair cells. Chemical inhibition or genetic mutation of the Chlamydomonas reinhardtii Arp2/3 complex decreases the length of flagella.{{Cite journal|last1=Avasthi|first1=Prachee|last2=Onishi|first2=Masayuki|last3=Karpiak|first3=Joel|last4=Yamamoto|first4=Ryosuke|last5=Mackinder|first5=Luke|last6=Jonikas|first6=Martin C.|last7=Sale|first7=Winfield S.|last8=Shoichet|first8=Brian|last9=Pringle|first9=John R.|last10=Marshall|first10=Wallace F.|date=September 2014|title=Actin Is Required for IFT Regulation in Chlamydomonas reinhardtii|url= |journal=Current Biology|volume=24|issue=17|pages=2025–2032|doi=10.1016/j.cub.2014.07.038|pmid=25155506|pmc=4160380|bibcode=2014CBio...24.2025A |issn=0960-9822}}{{Cite journal|last1=Bigge|first1=Brae M.|last2=Rosenthal|first2=Nicholas E.|last3=Sept|first3=David|last4=Schroeder|first4=Courtney M.|last5=Avasthi|first5=Prachee|date=2020-11-24|title=Initial ciliary assembly in Chlamydomonas requires Arp2/3-dependent recruitment from a ciliary protein reservoir in the plasma membrane|url=https://www.biorxiv.org/content/10.1101/2020.11.24.396002v1|journal=bioRxiv|language=en|pages=2020.11.24.396002|doi=10.1101/2020.11.24.396002|s2cid=233178920|doi-access=free}}

The Arp2/3 complex is composed of seven subunits: Arp2/ACTR2, Arp3/ACTR3, p41/ARPC1A&B/Arc40/Sop2/p40, p34/ARPC2/ARC35/p35, p21/ARPC3/ARC18/p19, p20/ARPC4/ARC19/p18, p16/ARPC5/ARC15/p14.{{Cite journal|last1=Pizarro-Cerdá|first1=Javier|last2=Chorev|first2=Dror Shlomo|last3=Geiger|first3=Benjamin|last4=Cossart|first4=Pascale|date=February 2017|title=The Diverse Family of Arp2/3 Complexes|url= |journal=Trends in Cell Biology|volume=27|issue=2|pages=93–100|doi=10.1016/j.tcb.2016.08.001|pmid=27595492|pmc=7098815|issn=0962-8924}} The subunits Arp2 and Arp3 closely resemble monomeric actin allowing for a thermodynamically stable actin-like dimer. p41 has been proposed to interact with nucleation promoting factors (NPFs) because it is only known to have minor contacts with the mother filament and there is a major loss of nucleation efficiency in the absence of p41. p34 and p20 dimerize to form a structural backbone that mediates the interaction with the mother filament. p21 forms a bridge between Arp3 and the mother filament, increasing nucleation efficiency. p16 tethers Arp2 to the rest of the complex.

Several subunits of the Arp2/3 complex exist in multiple isoforms, which can modulate its function, localization, and interactions in a context-dependent manner. For example, the ARPC1 subunit has two isoforms in mammals: ARPC1A and ARPC1B. Though they share considerable sequence similarity, they exhibit different expression patterns and functional roles. ARPC1B is predominantly expressed in hematopoietic cells, and its deficiency in humans has been associated with primary immunodeficiency characterized by thrombocytopenia, eczema, and increased susceptibility to infections, resembling Wiskott–Aldrich syndrome-like symptoms.{{Cite journal |last1=Kahr |first1=Walter H. A. |last2=Pluthero |first2=Fred G. |last3=Elkadri |first3=Abdul |last4=Warner |first4=Neil |last5=Drobac |first5=Marko |last6=Chen |first6=Chang Hua |last7=Lo |first7=Richard W. |last8=Li |first8=Ling |last9=Li |first9=Ren |last10=Li |first10=Qi |last11=Thoeni |first11=Cornelia |last12=Pan |first12=Jie |last13=Leung |first13=Gabriella |last14=Lara-Corrales |first14=Irene |last15=Murchie |first15=Ryan |date=2017-04-03 |title=Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease |journal=Nature Communications |language=en |volume=8 |issue=1 |pages=14816 |doi=10.1038/ncomms14816 |issn=2041-1723 |pmc=5382316 |pmid=28368018|bibcode=2017NatCo...814816K }}

Similarly, ARPC5 exists in two isoforms: ARPC5 and APRC5L (ARPC5-like). Recent studies suggest that these isoforms are not functionally redundant. ARPC5L has been implicated in driving increased actin nucleation activity, particularly in dynamic cellular regions such as lamellipodia, whereas ARPC5 appears to support more stable actin networks in less motile cells. These findings suggest that the specific isoform composition of the Arp2/3 complex determines its behavior in different cellular environments, including during cell migration, immune responses, and tissue morphogenesis.{{Cite journal |last1=Abella |first1=Jasmine V. G. |last2=Galloni |first2=Chiara |last3=Pernier |first3=Julien |last4=Barry |first4=David J. |last5=Kjær |first5=Svend |last6=Carlier |first6=Marie-France |last7=Way |first7=Michael |date=January 2016 |title=Isoform diversity in the Arp2/3 complex determines actin filament dynamics |url=https://www.nature.com/articles/ncb3286 |journal=Nature Cell Biology |language=en |volume=18 |issue=1 |pages=76–86 |doi=10.1038/ncb3286 |issn=1476-4679|url-access=subscription }}

Moreover, the dynamic incorporation of isoforms during development or in response to external stimuli suggests that the Arp2/3 complex operates as a modular machine, capable of tuning actin dynamics to suit specific cellular needs. Ongoing studies continue to investigate additional isoform-specific interactions and regulatory mechanisms that may further enhance our understanding of how actin networks are customized at the molecular level.{{Cite journal |last1=Jorstad |first1=Nikolas L. |last2=Wilken |first2=Matthew S. |last3=Todd |first3=Levi |last4=Finkbeiner |first4=Connor |last5=Nakamura |first5=Paul |last6=Radulovich |first6=Nicholas |last7=Hooper |first7=Marcus J. |last8=Chitsazan |first8=Alex |last9=Wilkerson |first9=Brent A. |last10=Rieke |first10=Fred |last11=Reh |first11=Thomas A. |date=2020-02-18 |title=STAT Signaling Modifies Ascl1 Chromatin Binding and Limits Neural Regeneration from Muller Glia in Adult Mouse Retina |journal=Cell Reports |language=English |volume=30 |issue=7 |pages=2195–2208.e5 |doi=10.1016/j.celrep.2020.01.075 |issn=2211-1247 |pmc=7148114 |pmid=32075759}}

The Arp2/3 complex is composed of seven subunits: two actin-related proteins (Arp2 and Arp3) and five additional subunits (ARPC1–ARPC5). In its inactive state, the complex adopts a compact conformation where Arp2 and Arp3 are spatially separated and not aligned in a way that mimics an actin dimer. This conformation prevents spontaneous actin nucleation.{{Cite journal |last1=Robinson |first1=Robert C. |last2=Turbedsky |first2=Kirsi |last3=Kaiser |first3=Donald A. |last4=Marchand |first4=Jean-Baptiste |last5=Higgs |first5=Henry N. |last6=Choe |first6=Senyon |last7=Pollard |first7=Thomas D. |date=2001-11-23 |title=Crystal Structure of Arp2/3 Complex |url=https://www.science.org/doi/10.1126/science.1066333 |journal=Science |volume=294 |issue=5547 |pages=1679–1684 |doi=10.1126/science.1066333|pmid=11721045 |bibcode=2001Sci...294.1679R |url-access=subscription }}

Upon activation by nucleation-promoting factors (NPFs)—such as WASP, WAVE, and WASH—the Arp2/3 complex undergoes a dramatic conformational rearrangement. Cryo-electron microscopy (cryo-EM) and molecular dynamics simulations have revealed that the binding of NPFs and ATP induces repositioning of Arp2 and Arp3 into a short-pitch actin-like dimer, the geometry required for nucleating a new actin filament branch.{{Cite journal |last1=Shaaban |first1=Mohammed |last2=Chowdhury |first2=Saikat |last3=Nolen |first3=Brad J. |date=November 2020 |title=Cryo-EM reveals the transition of Arp2/3 complex from inactive to nucleation-competent state |journal=Nature Structural & Molecular Biology |language=en |volume=27 |issue=11 |pages=1009–1016 |doi=10.1038/s41594-020-0481-x |pmc=8717925 |issn=1545-9985}}{{Cite journal |last1=Stagi |first1=Massimiliano |last2=Fogel |first2=Adam I. |last3=Biederer |first3=Thomas |date=2010-04-20 |title=SynCAM 1 participates in axo-dendritic contact assembly and shapes neuronal growth cones |journal=Proceedings of the National Academy of Sciences |volume=107 |issue=16 |pages=7568–7573 |doi=10.1073/pnas.0911798107 |doi-access=free |pmc=2867738 |pmid=20368431|bibcode=2010PNAS..107.7568S }}This transition forms a structural "template" that resembles a barbed-end actin nucleus, which then elongates by recruiting actin monomers.

The core subunits, particularly ARPC2 and ARPC4, form a structural scaffold that binds the side of an existing ("mother") actin filament at a 70-degree angle. This binding provides the platform from which a new ("daughter") filament can branch.{{Cite journal |last1=Rouiller |first1=Isabelle |last2=Xu |first2=Xiao-Ping |last3=Amann |first3=Kurt J. |last4=Egile |first4=Coumaran |last5=Nickell |first5=Stephan |last6=Nicastro |first6=Daniela |last7=Li |first7=Rong |last8=Pollard |first8=Thomas D. |last9=Volkmann |first9=Niels |last10=Hanein |first10=Dorit |date=2008-03-03 |title=The structural basis of actin filament branching by the Arp2/3 complex |url=https://rupress.org/jcb/article/180/5/887/45217/The-structural-basis-of-actin-filament-branching |journal=Journal of Cell Biology |volume=180 |issue=5 |pages=887–895 |doi=10.1083/jcb.200709092 |issn=0021-9525 |pmc=2265399 |pmid=18316411}} Structural data show that ATP binding is essential for this transition. Arp2 and Arp3 bind ATP, and their hydrolysis states may regulate both activation and deactivation of the complex, influencing filament stability over time.{{Cite journal |last1=Williams |first1=R. Scott |last2=Lee |first2=Megan S. |last3=Hau |first3=D. Duong |last4=Glover |first4=J. N. Mark |date=April 2004 |title=Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1 |url=https://www.nature.com/articles/nsmb776 |journal=Nature Structural & Molecular Biology |language=en |volume=11 |issue=6 |pages=519–525 |doi=10.1038/nsmb776 |pmid=15133503 |hdl=1807.1/533 |issn=1545-9985|hdl-access=free }}

Recent high-resolution cryo-EM studies have further refined our understanding by capturing the Arp2/3 complex at different stages of the activation cycle. These structures demonstrate a multi-step activation mechanism, starting from NPF binding, through ATP-dependent conformational change, to the final stabilization of the branch junction.{{Cite journal |last1=Jorstad |first1=Nikolas L. |last2=Wilken |first2=Matthew S. |last3=Todd |first3=Levi |last4=Finkbeiner |first4=Connor |last5=Nakamura |first5=Paul |last6=Radulovich |first6=Nicholas |last7=Hooper |first7=Marcus J. |last8=Chitsazan |first8=Alex |last9=Wilkerson |first9=Brent A. |last10=Rieke |first10=Fred |last11=Reh |first11=Thomas A. |date=2020-02-18 |title=STAT Signaling Modifies Ascl1 Chromatin Binding and Limits Neural Regeneration from Muller Glia in Adult Mouse Retina |journal=Cell Reports |language=English |volume=30 |issue=7 |pages=2195–2208.e5 |doi=10.1016/j.celrep.2020.01.075 |issn=2211-1247 |pmc=7148114 |pmid=32075759}} Importantly, these studies also highlight the flexibility and heterogeneity of Arp2/3 complexes in different cellular contexts, suggesting that isoform composition and regulatory protein interactions can subtly alter the conformational landscape and activity profile of the complex.

Additionally, structural studies have shown that phosphoinositides, such as PIP2, can modulate the activity of the Arp2/3 complex by altering its interaction with upstream activators. This indicates that lipid signaling is also structurally integrated into Arp2/3 regulation.{{Cite journal |last1=Lau |first1=Alan |last2=Swinbank |first2=Karra M. |last3=Ahmed |first3=Parvin S. |last4=Taylor |first4=Debra L. |last5=Jackson |first5=Stephen P. |last6=Smith |first6=Graeme C. M. |last7=O'Connor |first7=Mark J. |date=May 2005 |title=Suppression of HIV-1 infection by a small molecule inhibitor of the ATM kinase |url=https://www.nature.com/articles/ncb1250 |journal=Nature Cell Biology |language=en |volume=7 |issue=5 |pages=493–500 |doi=10.1038/ncb1250 |pmid=15834407 |issn=1476-4679|url-access=subscription }}

The Arp2/3 complex is essential for the spatial and temporal regulation of actin cytoskeleton dynamics, playing a central role in numerous fundamental cellular processes. Its ability to nucleate branched actin filaments allows cells to generate protrusive forces, organize membrane architecture, and support a range of activities critical for survival, communication, and development.

One of the most well-characterized roles of the Arp2/3 complex is in cell motility, particularly through the formation of lamellipodia, sheet-like protrusions at the leading edge of migrating cells.{{Cite journal |last=Cox |first=Michael M. |date=2003-02-07 |title=Better Chemistry for Better Survival, through Regulation |url=https://linkinghub.elsevier.com/retrieve/pii/S0092867403000801 |journal=Cell |language=English |volume=112 |issue=3 |pages=286–287 |doi=10.1016/S0092-8674(03)00080-1 |pmid=12581518 |issn=0092-8674}} This is vital in processes such as embryonic development, immune cell trafficking, and wound healing. The complex, activated by nucleation-promoting factors like WASP and WAVE, catalyzes the branching of actin filaments to push the plasma membrane forward.{{Cite journal |last1=Takenawa |first1=Tadaomi |last2=Suetsugu |first2=Shiro |date=January 2007 |title=The WASP–WAVE protein network: connecting the membrane to the cytoskeleton |url=https://www.nature.com/articles/nrm2069 |journal=Nature Reviews Molecular Cell Biology |language=en |volume=8 |issue=1 |pages=37–48 |doi=10.1038/nrm2069 |pmid=17183359 |issn=1471-0080|url-access=subscription }}

In neuronal development, the Arp2/3 complex plays a pivotal role in axon guidance, neurite outgrowth, and dendritic spine formation. Disruption of Arp2/3 function in mouse models leads to severe abnormalities in the cortical layering of neurons, loss of neuronal polarity, and impaired synaptic plasticity, indicating that actin nucleation is critical for establishing and maintaining neural networks.{{Cite journal |last1=Wang |first1=Pei-Shan |last2=Chou |first2=Fu-Sheng |last3=Ramachandran |first3=Sreekumar |last4=Xia |first4=Sheng |last5=Chen |first5=Huei-Ying |last6=Guo |first6=Fengli |last7=Suraneni |first7=Praveen |last8=Maher |first8=Brady J. |last9=Li |first9=Rong |date=2016-08-01 |title=Crucial roles of the Arp2/3 complex during mammalian corticogenesis |journal=Development |volume=143 |issue=15 |pages=2741–2752 |doi=10.1242/dev.130542 |issn=0950-1991 |pmc=5004905 |pmid=27385014}}{{Cite journal |last1=Takagi |first1=Yasuharu |last2=Yang |first2=Yi |last3=Fujiwara |first3=Ikuko |last4=Jacobs |first4=Damon |last5=Cheney |first5=Richard E. |last6=Sellers |first6=James R. |last7=Kovács |first7=Mihály |date=2008-03-28 |title=Human Myosin Vc Is a Low Duty Ratio, Nonprocessive Molecular Motor * |journal=Journal of Biological Chemistry |language=English |volume=283 |issue=13 |pages=8527–8537 |doi=10.1074/jbc.M709150200 |doi-access=free |issn=0021-9258 |pmid=18201966|hdl=10831/92866 |hdl-access=free }}

The complex is also integral to endocytosis and intracellular trafficking. It facilitates the deformation of membranes during clathrin-mediated endocytosis by generating branched actin networks that drive membrane invagination and vesicle scission.{{Cite journal |last1=Chekulaeva |first1=Marina |last2=Filipowicz |first2=Witold |date=2009-06-01 |title=Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells |url=https://linkinghub.elsevier.com/retrieve/pii/S0955067409000957 |journal=Current Opinion in Cell Biology |series=Nucleus and gene expression |volume=21 |issue=3 |pages=452–460 |doi=10.1016/j.ceb.2009.04.009 |pmid=19450959 |issn=0955-0674|url-access=subscription }} In yeast and mammalian cells, Arp2/3-dependent actin polymerization is required for vesicle propulsion and the recycling of membrane components, making it essential for nutrient uptake and receptor turnover.{{Cite journal |last1=Field |first1=Mark C |last2=Dacks |first2=Joel B |date=2009-02-01 |title=First and last ancestors: reconstructing evolution of the endomembrane system with ESCRTs, vesicle coat proteins, and nuclear pore complexes |url=https://linkinghub.elsevier.com/retrieve/pii/S0955067408001993 |journal=Current Opinion in Cell Biology |series=Cell structure and dynamics |volume=21 |issue=1 |pages=4–13 |doi=10.1016/j.ceb.2008.12.004 |issn=0955-0674|url-access=subscription }}

In epithelial tissues, the Arp2/3 complex contributes to cell-cell adhesion, apical-basal polarity, and tight junction maintenance. Its activity supports the formation of microvilli and filopodia, ensuring proper barrier function and nutrient absorption.{{Cite journal |last1=Zihni |first1=Ceniz |last2=Mills |first2=Clare |last3=Matter |first3=Karl |last4=Balda |first4=Maria S. |date=September 2016 |title=Tight junctions: from simple barriers to multifunctional molecular gates |url=https://www.nature.com/articles/nrm.2016.80 |journal=Nature Reviews Molecular Cell Biology |language=en |volume=17 |issue=9 |pages=564–580 |doi=10.1038/nrm.2016.80 |pmid=27353478 |issn=1471-0080}} Genetic knockdown studies in intestinal epithelial cells have shown that loss of Arp2/3 activity leads to compromised epithelial integrity and altered morphogenesis.{{Cite journal |last1=Whittamore |first1=Jonathan M. |last2=Freel |first2=Robert W. |last3=Hatch |first3=Marguerite |date=2013-07-15 |title=Sulfate secretion and chloride absorption are mediated by the anion exchanger DRA (Slc26a3) in the mouse cecum |journal=American Journal of Physiology-Gastrointestinal and Liver Physiology |volume=305 |issue=2 |pages=G172–G184 |doi=10.1152/ajpgi.00084.2013 |issn=0193-1857 |pmc=3725685 |pmid=23660504}}

In the immune system, Arp2/3-mediated actin remodeling is necessary for phagocytosis, immune synapse formation, and migration of leukocytes. During antigen presentation, dendritic cells utilize Arp2/3 to form dynamic actin-rich protrusions that increase surface area and facilitate T-cell interactions. Moreover, ARPC1B deficiency in humans has been linked to severe combined immunodeficiency, further underscoring the critical role of Arp2/3 in immune homeostasis.{{Cite journal |last1=Kahr |first1=Walter H. A. |last2=Pluthero |first2=Fred G. |last3=Elkadri |first3=Abdul |last4=Warner |first4=Neil |last5=Drobac |first5=Marko |last6=Chen |first6=Chang Hua |last7=Lo |first7=Richard W. |last8=Li |first8=Ling |last9=Li |first9=Ren |last10=Li |first10=Qi |last11=Thoeni |first11=Cornelia |last12=Pan |first12=Jie |last13=Leung |first13=Gabriella |last14=Lara-Corrales |first14=Irene |last15=Murchie |first15=Ryan |date=2017-04-03 |title=Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease |journal=Nature Communications |language=en |volume=8 |issue=1 |pages=14816 |doi=10.1038/ncomms14816 |issn=2041-1723 |pmc=5382316 |pmid=28368018|bibcode=2017NatCo...814816K }}

Beyond normal physiology, the Arp2/3 complex is implicated in pathological conditions, such as cancer. Many tumors exhibit upregulated Arp2/3 expression, correlating with increased invasiveness and metastatic potential. The complex promotes invadopodia formation, which are actin-rich protrusions that degrade extracellular matrix and facilitate tumor cell dissemination.{{Cite journal |last=Teitell |first=Michael A. |date=September 2005 |title=Erratum: The TCL1 family of oncoproteins: co-activators of transformation |url=https://www.nature.com/articles/nrc1711 |journal=Nature Reviews Cancer |language=en |volume=5 |issue=9 |pages=750 |doi=10.1038/nrc1711 |issn=1474-1768}}

{{reflist|32em|refs =

{{cite journal | vauthors = Robinson RC, Turbedsky K, Kaiser DA, Marchand JB, Higgs HN, Choe S, Pollard TD | s2cid = 18088124 | title = Crystal structure of Arp2/3 complex | journal = Science | volume = 294 | issue = 5547 | pages = 1679–84 | date = November 2001 | pmid = 11721045 | doi = 10.1126/science.1066333 | bibcode = 2001Sci...294.1679R }}

{{cite journal | vauthors = Pollard TD | title = Regulation of actin filament assembly by Arp2/3 complex and formins | journal = Annual Review of Biophysics and Biomolecular Structure | volume = 36 | pages = 451–77 | year = 2007 | pmid = 17477841 | doi = 10.1146/annurev.biophys.35.040405.101936 }}

{{cite journal | vauthors = Aguda AH, Burtnick LD, Robinson RC | title = The state of the filament | journal = EMBO Reports | volume = 6 | issue = 3 | pages = 220–6 | date = March 2005 | pmid = 15741975 | pmc = 1299273 | doi = 10.1038/sj.embor.7400363 }}

{{cite journal | vauthors = Egile C, Rouiller I, Xu XP, Volkmann N, Li R, Hanein D | title = Mechanism of filament nucleation and branch stability revealed by the structure of the Arp2/3 complex at actin branch junctions | journal = PLOS Biology | volume = 3 | issue = 11 | pages = e383 | date = November 2005 | pmid = 16262445 | pmc = 1278936 | doi = 10.1371/journal.pbio.0030383 | doi-access = free }}

{{cite journal | vauthors = Bannigan A, Baskin TI | title = Directional cell expansion--turning toward actin | journal = Current Opinion in Plant Biology | volume = 8 | issue = 6 | pages = 619–24 | date = December 2005 | pmid = 16181803 | doi = 10.1016/j.pbi.2005.09.002 | bibcode = 2005COPB....8..619B | url = https://scholarworks.umass.edu/cgi/viewcontent.cgi?article=1018&context=biology_faculty_pubs }}

{{cite journal | vauthors = Mathur J | title = The ARP2/3 complex: giving plant cells a leading edge | journal = BioEssays | volume = 27 | issue = 4 | pages = 377–87 | date = April 2005 | pmid = 15770684 | doi = 10.1002/bies.20206 | s2cid = 423293 }}

{{cite journal | vauthors = Xu J, Scheres B | title = Cell polarity: ROPing the ends together | journal = Current Opinion in Plant Biology | volume = 8 | issue = 6 | pages = 613–8 | date = December 2005 | pmid = 16182602 | doi = 10.1016/j.pbi.2005.09.003 | bibcode = 2005COPB....8..613X | hdl = 1874/21120 | s2cid = 23098801 | hdl-access = free }}

{{cite journal | vauthors = Warren DT, Andrews PD, Gourlay CW, Ayscough KR | title = Sla1p couples the yeast endocytic machinery to proteins regulating actin dynamics | journal = Journal of Cell Science | volume = 115 | issue = Pt 8 | pages = 1703–15 | date = April 2002 | doi = 10.1242/jcs.115.8.1703 | pmid = 11950888 | url = http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=11950888 | url-access = subscription | doi-access = free }}

{{cite journal | vauthors = May RC, Caron E, Hall A, Machesky LM | title = Involvement of the Arp2/3 complex in phagocytosis mediated by FcgammaR or CR3 | journal = Nature Cell Biology | volume = 2 | issue = 4 | pages = 246–8 | date = April 2000 | pmid = 10783245 | doi = 10.1038/35008673 | s2cid = 33742268 }}

{{cite journal | vauthors = Insall R, Müller-Taubenberger A, Machesky L, Köhler J, Simmeth E, Atkinson SJ, Weber I, Gerisch G | title = Dynamics of the Dictyostelium Arp2/3 complex in endocytosis, cytokinesis, and chemotaxis | journal = Cell Motility and the Cytoskeleton | volume = 50 | issue = 3 | pages = 115–28 | date = November 2001 | pmid = 11807934 | doi = 10.1002/cm.10005 }}

{{cite journal | vauthors = Magdalena J, Millard TH, Etienne-Manneville S, Launay S, Warwick HK, Machesky LM | title = Involvement of the Arp2/3 complex and Scar2 in Golgi polarity in scratch wound models | journal = Molecular Biology of the Cell | volume = 14 | issue = 2 | pages = 670–84 | date = February 2003 | pmid = 12589062 | pmc = 150000 | doi = 10.1091/mbc.E02-06-0345 }}

{{cite journal | vauthors = Volkmann N, Amann KJ, Stoilova-McPhie S, Egile C, Winter DC, Hazelwood L, Heuser JE, Li R, Pollard TD, Hanein D | title = Structure of Arp2/3 complex in its activated state and in actin filament branch junctions | journal = Science | volume = 293 | issue = 5539 | pages = 2456–9 | date = September 2001 | pmid = 11533442 | doi = 10.1126/science.1063025 | bibcode = 2001Sci...293.2456V | s2cid = 17427295 | doi-access = free }}

{{cite journal | vauthors = Dayel MJ, Mullins RD | title = Activation of Arp2/3 complex: addition of the first subunit of the new filament by a WASP protein triggers rapid ATP hydrolysis on Arp2 | journal = PLOS Biology | volume = 2 | issue = 4 | pages = E91 | date = April 2004 | pmid = 15094799 | pmc = 387265 | doi = 10.1371/journal.pbio.0020091 | doi-access = free }}

{{cite journal | vauthors = Machesky LM, Atkinson SJ, Ampe C, Vandekerckhove J, Pollard TD | title = Purification of a cortical complex containing two unconventional actins from Acanthamoeba by affinity chromatography on profilin-agarose | journal = The Journal of Cell Biology | volume = 127 | issue = 1 | pages = 107–15 | date = October 1994 | pmid = 7929556 | pmc = 2120189 | doi = 10.1083/jcb.127.1.107 }}

{{cite journal | vauthors = Miller KG, Field CM, Alberts BM | title = Actin-binding proteins from Drosophila embryos: a complex network of interacting proteins detected by F-actin affinity chromatography | journal = The Journal of Cell Biology | volume = 109 | issue = 6 Pt 1 | pages = 2963–75 | date = December 1989 | pmid = 2512303 | pmc = 2115944 | doi = 10.1083/jcb.109.6.2963 }}

{{cite journal | vauthors = Veltman DM, Insall RH | title = WASP family proteins: their evolution and its physiological implications | journal = Molecular Biology of the Cell | volume = 21 | issue = 16 | pages = 2880–93 | date = August 2010 | pmid = 20573979 | pmc = 2921111 | doi = 10.1091/mbc.E10-04-0372 }}

{{cite journal | vauthors = Pantaloni D, Boujemaa R, Didry D, Gounon P, Carlier MF | title = The Arp2/3 complex branches filament barbed ends: functional antagonism with capping proteins | journal = Nature Cell Biology | volume = 2 | issue = 7 | pages = 385–91 | date = July 2000 | pmid = 10878802 | doi = 10.1038/35017011 | s2cid = 28209883 }}

{{cite journal | vauthors = Rouiller I, Xu XP, Amann KJ, Egile C, Nickell S, Nicastro D, Li R, Pollard TD, Volkmann N, Hanein D | title = The structural basis of actin filament branching by the Arp2/3 complex | journal = The Journal of Cell Biology | volume = 180 | issue = 5 | pages = 887–95 | date = March 2008 | pmid = 18316411 | pmc = 2265399 | doi = 10.1083/jcb.200709092 }}

{{cite journal | vauthors = Yi K, Unruh JR, Deng M, Slaughter BD, Rubinstein B, Li R | title = Dynamic maintenance of asymmetric meiotic spindle position through Arp2/3-complex-driven cytoplasmic streaming in mouse oocytes | journal = Nature Cell Biology | volume = 13 | issue = 10 | pages = 1252–8 | date = August 2011 | pmid = 21874009 | pmc = 3523671 | doi = 10.1038/ncb2320 }}

{{cite journal | vauthors = Cossart P | title = Actin-based motility of pathogens: the Arp2/3 complex is a central player | journal = Cellular Microbiology | volume = 2 | issue = 3 | pages = 195–205 | date = June 2000 | pmid = 11207576 | doi=10.1046/j.1462-5822.2000.00053.x| s2cid = 44343534 | doi-access = free }}

{{cite journal | vauthors = Goley ED, Welch MD | title = The ARP2/3 complex: an actin nucleator comes of age | journal = Nature Reviews Molecular Cell Biology | volume = 7 | issue = 10 | pages = 713–26 | date = October 2006 | pmid = 16990851 | doi = 10.1038/nrm2026 | s2cid = 20645116 | doi-access = free }}

{{cite journal | vauthors = Pizarro-Cerdá J, Chorev DS, Geiger B, Cossart P | title = The Diverse Family of Arp2/3 Complexes | journal = Trends in Cell Biology | volume = 27 | issue = 2 | pages = 93–100 | date = February 2017 | pmid = 27595492 | doi = 10.1016/j.tcb.2016.08.001 | pmc = 7098815 | url = https://hal-pasteur.archives-ouvertes.fr/pasteur-01457856/file/Figure%201.pdf }}

}}

• [http://www.mechanobio.info/modules/go-0045010#3_go-0045010 MBInfo - Arp2/3 Mediated Nucleation]
• {{MeshName|Arp2-3+Complex}}
• [http://www.dayel.com/research/arp23-complex/ Arp2/3 filament nucleation model, illustrated with 2D animations and 3D structure-based movies]

{{Cytoskeletal Proteins}}

{{good article}}

{{DEFAULTSORT:Arp2 3 complex}}

Category:Cytoskeleton proteins

Category:Protein complexes