| 1997 |
ARPC3 (p21-Arc) was identified as one of seven subunits of the human Arp2/3 complex; p21-Arc, Arp3, and p34-Arc were localized to lamellipodia of stationary and locomoting fibroblasts and to Listeria monocytogenes actin tails, but not to actin stress fibers, establishing the complex's role in dynamic actin assembly at the leading edge. |
Protein complex purification, sequence determination, immunofluorescence localization in cells and Listeria-infected cells |
The Journal of cell biology |
High |
9230079
|
| 2001 |
Crystal structure of bovine Arp2/3 complex at 2.0 Å resolution revealed ARPC3 (p21) as a globular alpha-helical subunit positioned in the complex; structural analysis predicted that WASp/Scar proteins activate the complex by repositioning Arp2 near Arp3 for actin filament branch nucleation. |
X-ray crystallography (2.0 Å resolution) |
Science (New York, N.Y.) |
High |
11721045
|
| 2001 |
RNAi knockdown of ARC21 (ARPC3) in mammalian cultured cells caused impaired cell growth, identifying ARPC3 as an essential gene for cell viability in tissue culture. |
siRNA-mediated knockdown, immunofluorescence, immunoblotting, cell growth assay |
Journal of cell science |
Medium |
11792820
|
| 2001 |
Yeast two-hybrid analysis of human Arp2/3 subunits showed that p21-Arc (ARPC3) directly interacts with p20-Arc (ARPC4); structural integrity was important for the p20-Arc/p21-Arc association, suggesting a specific assembly interface between these subunits. |
Yeast two-hybrid assay |
Biochemical and biophysical research communications |
Low |
11162547
|
| 2000 |
Immunofluorescence with anti-p21-Arc (ARPC3) antibodies showed that the initial recruitment of the Arp2/3 complex to the surface of Listeria monocytogenes requires arginine residues within the 146-KKRRK-150 motif of ActA, and that this recruitment precedes and is independent of actin polymerization. |
Site-directed mutagenesis of ActA, immunofluorescence with anti-p21-Arc antibody, latrunculin B treatment |
Journal of cell science |
Medium |
10954425
|
| 2005 |
NMR spectroscopy using site-directed spin labeling and methyl-TROSY, combined with chemical cross-linking, identified that the extreme C-terminus of the A region and the C-terminus of the C region of N-WASP VCA are proximal to ARPC3 in the Arp2/3 complex, implicating ARPC3 in the binding interface for activating NPFs. |
Site-directed spin labeling, methyl-TROSY NMR, chemical cross-linking/MS |
Biochemistry |
High |
16285728
|
| 2006 |
Tiam1 (a Rac-GEF) interacts directly with the p21-Arc (ARPC3) subunit of the Arp2/3 complex via its N-terminal pleckstrin homology domain and adjacent coiled-coil region; this interaction co-localizes Tiam1 with the Arp2/3 complex at sites of actin polymerization, and deletion of the p21-Arc-binding domain in Tiam1 impairs its subcellular localization and capacity to activate Rac1. |
Yeast two-hybrid screening, co-immunoprecipitation, biochemical pulldown, immunofluorescence co-localization, deletion mutagenesis |
The Biochemical journal |
High |
16599904
|
| 2006 |
Homozygous disruption of the Arpc3 gene (Sleeping Beauty transposon insertion) in mice results in embryonic lethality at the blastocyst stage; in vitro culture shows severe trophoblast spreading impairment with loss of actin-rich structures and absence of mesh-like (Y-branched) actin at the cell periphery, demonstrating that ARPC3 is required for Y-branch actin formation and trophoblast outgrowth. |
Transposon insertional mutagenesis, conventional gene targeting, in vitro blastocyst culture, immunofluorescence, electron microscopy |
Molecular and cellular biology |
High |
16880528
|
| 2010 |
Molecular dynamics simulations of the inactive Arp2/3 crystal structure showed that ARPC3 and the globular domains of ARPC2 form one structural block while Arp2, ARPC1, ARPC4 globular domain, and ARPC5 form another; the activation conformational change involves rotation of the second block around an ARPC4 alpha-helix pivot, with ARPC3 remaining in its block throughout the transition. |
Atomistic molecular dynamics simulation based on crystal structure |
Biophysical journal |
Low |
20959098
|
| 2011 |
RNAi-mediated knockdown of Arpc3 (and Arpc2) in mouse oocytes disrupted asymmetric division, spindle migration, formation of the actin cap and cortical granule-free domain, and completion of cytokinesis during meiotic maturation, establishing ARPC3 as required for oocyte polarization and asymmetric cell division. |
siRNA microinjection, immunofluorescence, live imaging in mouse oocytes; pharmacological inhibition with CK666 |
PloS one |
Medium |
21494665
|
| 2011 |
miR-29a/b directly target the 3'UTR of Arpc3 mRNA in hippocampal neurons; overexpression of miR-29a/b reduces Arpc3 protein levels and converts mushroom-shaped dendritic spines to filopodial-like protrusions, demonstrating that ARPC3 is a downstream effector of miR-29a/b in regulating actin network branching and spine morphology. |
Luciferase reporter assay (3'UTR targeting), Western blotting, in vitro imaging of dendritic spines in hippocampal neurons |
The Journal of cell biology |
High |
21930776
|
| 2011 |
S. pombe arc3 (ortholog of human ARPC3) is essential for viability; depletion causes dispersal of F-actin patches with reduced mobility and inhibits endocytosis. Human ARPC3 complemented the viability defect of the arc3 null mutant and localized to F-actin patches, demonstrating functional conservation. |
Gene deletion, conditional expression repression, F-actin imaging, endocytosis assay, cross-species complementation |
Yeast (Chichester, England) |
High |
21449051
|
| 2012 |
Nucleation promoting factors JMY and WAVE2 act upstream of the Arp2/3 complex in mouse oocytes; knockdown of Arpc2 or Arpc3 did not affect JMY or WAVE2 expression or localization, establishing that NPFs are upstream regulators of ARPC3-containing Arp2/3 complex during oocyte asymmetric division. |
siRNA knockdown of Arpc2 and Arpc3, immunofluorescence, Western blotting in mouse oocytes |
PloS one |
Medium |
23272233
|
| 2012 |
Fibroblasts derived from ARPC3-/- mouse embryonic stem cells lack lamellipodia but form filopodia-like protrusions with formins (mDia1/mDia2) at their tips; these cells show normal migration speed but a strong defect in persistent directional migration due to uncoordinated leading-edge protrusion. |
Genetic knockout (isogenic ES cell differentiation), live-cell imaging, immunofluorescence, migration assays |
The Journal of cell biology |
High |
22492726
|
| 2013 |
Conditional postnatal knockout of ArpC3 in forebrain excitatory neurons causes asymmetric structural plasticity of dendritic spines followed by progressive loss of spine synapses, accompanied by cognitive, psychomotor, and social disturbances, demonstrating that ARPC3-dependent actin polymerization is required for maintaining dendritic spine structure and synaptic function. |
Conditional knockout mouse (Cre-lox), electron microscopy, immunofluorescence, behavioral testing |
The Journal of neuroscience : the official journal of the Society for Neuroscience |
High |
23554489
|
| 2013 |
Loss of ArpC3 in the epidermis results in defective tight junction assembly/function and impaired terminal differentiation into cornified envelopes; YAP was found to be inappropriately active in ArpC3-mutant tissue, and YAP inhibition rescued both differentiation and barrier defects, placing ARPC3/Arp2/3 upstream of YAP in epidermal barrier formation. |
Conditional knockout mouse (epidermis-specific), barrier assays, immunofluorescence, YAP inhibition rescue experiment |
Proceedings of the National Academy of Sciences of the United States of America |
High |
24043783
|
| 2015 |
In ARPC3-null fibroblasts, formin-family nucleators are required for filopodia-like protrusion extension but are insufficient to produce a continuous leading edge; myosin II activity is required for coordinated advancement of inter-FLP arc regions, explaining the directional migration defect in Arpc3-null cells. |
Genetic knockout fibroblasts, pharmacological inhibition of formins and myosin II, live-cell imaging, mathematical modeling with experimental verification |
Molecular biology of the cell |
High |
25568333
|
| 2015 |
Loss of ArpC3 in intestinal enterocytes disrupts the endolysosomal system organization without affecting cortical F-actin or cell polarity; this impairs transcytosis of IgG and lipid absorption, demonstrating that the Arp2/3 complex's role in vesicle trafficking rather than cortical actin underlies intestinal phenotypes. |
Intestine-specific conditional knockout mouse, subcellular fractionation, transcytosis assay, lipid absorption assay, immunofluorescence |
Molecular biology of the cell |
High |
25833710
|
| 2014 |
Knockdown of ARPC3 (or Arp3) strongly impaired adipocyte differentiation; Arp2/3 complex is required for the assembly of cortical F-actin structures at the plasma membrane during adipogenesis, which in turn are essential for GLUT4 vesicle exocytosis and insulin signal transduction. |
siRNA knockdown, F-actin imaging, GLUT4 exocytosis assay, insulin signaling assay in differentiating adipocytes |
The Biochemical journal |
Medium |
25220164
|
| 2020 |
Cryo-electron tomography of branch junctions in cells at 9 Å resolution revealed a new set of interactions between the Arp2/3 complex and the mother actin filament; ARPC3 plays a central structural role in stabilizing the active conformation of the complex within the branch junction. |
Cryo-electron tomography, subtomogram averaging (9.0 Å resolution), in-cell structure determination |
Nature communications |
High |
33353942
|
| 2020 |
Loss or inhibition of mTOR in oligodendrocyte precursor cells reduced ARPC3 expression along with profilin2, and elevated active cofilin, resulting in defective actin polymerization, reduced cellular branching, and delayed myelination initiation, placing ARPC3 downstream of mTOR in oligodendrocyte differentiation. |
Conditional knockout of mTOR in oligodendrocytes, Western blotting, phalloidin staining, morphological analysis |
The Journal of neuroscience : the official journal of the Society for Neuroscience |
Medium |
32139584
|
| 2020 |
Circuit-selective knockout of ArpC3 in prefrontal cortical neurons projecting to the basolateral amygdala elevates neuronal excitability, disrupts socially evoked neural activity, and causes abnormal social behavior; optogenetic silencing of this circuit rescues the behavioral deficit, establishing a gene-to-circuit mechanism. |
Circuit-selective conditional knockout (Cre-lox with retrograde viral vectors), in vivo electrophysiology, optogenetics, behavioral assays |
Cell reports |
High |
32726629
|
| 2017 |
ARPC3 interacts with IFT20 (an intraflagellar transport component) in T cells; RNAi depletion of ARPC3 impairs TCR accumulation and phosphotyrosine signaling at the immune synapse due to failure of endosomal TCR polarization, despite correct centrosome translocation. |
Quantitative mass spectrometry interactome, RNAi knockdown, confocal imaging of immune synapses in antigen-specific T cell conjugates |
Journal of cell science |
Medium |
28154159
|
| 2019 |
miR-124-5p directly targets the 3'UTR of ARPC3 (and ARPC4) mRNA, as confirmed by luciferase reporter assay; transfection of miR-124-5p mimics reduces ARPC3 and ARPC4 protein levels and suppresses phagocytosis in THP-1 macrophages and primary human macrophages. |
Luciferase reporter assay, Western blotting, transfection of miRNA mimics, phagocytosis assay |
Frontiers in immunology |
High |
31636629
|
| 2023 |
Nuclear cGAS induced by VEGF-A stimulation regulates ARPC3 expression via a miR-212-5p-ARPC3 cascade; this modulates VEGF-A-mediated angiogenesis through cytoskeletal dynamics and VEGFR2 trafficking from the trans-Golgi network to the plasma membrane. |
Nuclear fractionation, overexpression/knockdown of cGAS, miRNA mimics/inhibitors, VEGFR2 trafficking assay, in vitro and in vivo angiogenesis assays |
Cell reports |
Medium |
37027305
|
| 2024 |
Genetic depletion of ArpC3 in alveolar type 2 cells (AT2s) inhibits AT2 migration between alveolar units following lung injury, leading to impaired regeneration of both AT2 and AT1 cells in vivo, establishing ARPC3-dependent migration as required for lung stem cell-mediated repair. |
Conditional genetic knockout, longitudinal intravital imaging, in vivo lung injury and regeneration assays |
Developmental cell |
High |
38377991
|
| 2025 |
ARPC3 is identified as a direct target of miR-26a-5p in extravillous trophoblasts (EVTs); ARPC3 knockdown mimics miR-26a-5p overexpression by disrupting actin cytoskeletal organization (converting lamellipodia to filopodia at leading edges) and impairing EVT invasion and migration. Ectopic ARPC3 expression rescues the invasion/migration defects caused by miR-26a-5p overexpression. |
miRNA mimic/inhibitor transfection, ARPC3 knockdown, ARPC3 overexpression rescue, immunofluorescence of F-actin, Transwell invasion assay, placental explant outgrowth assay |
Biology of reproduction |
High |
40626921
|
| 2022 |
The cytoplasmic tail motif V1264L1265 of the SARS-CoV-2 spike protein interacts with ARPC3; reducing ARPC3 expression significantly repressed live SARS-CoV-2 virion assembly, identifying ARPC3 as a host factor required for viral assembly. |
Co-immunoprecipitation, siRNA knockdown of ARPC3, live SARS-CoV-2 and pseudovirus assembly assays |
Antiviral research |
Medium |
36572190
|
| 2016 |
Chemical cross-linking/mass spectrometry identified direct protein-protein interactions between PKD2 (protein kinase D2) and all seven subunits of the Arp2/3 complex including ARPC3, in both cytosolic and Golgi-enriched fractions, suggesting PKD2 interacts with ARPC3-containing Arp2/3 at the trans-Golgi network. |
Affinity enrichment, chemical cross-linking, mass spectrometry |
Journal of proteome research |
Medium |
27559607
|
| 2025 |
CKI (and its active component matrine) inhibit breast cancer lung metastasis by upregulating MTSS1 and downregulating ARPC3 expression, altering F-actin structure, and inhibiting EMT; ARPC3 is placed downstream of MTSS1 in a pathway regulating actin-based cancer cell invasion. |
Proteomic analysis, Western blotting, immunohistochemistry, immunofluorescence of F-actin, Transwell invasion assay, in vivo tumor/metastasis model |
Journal of ethnopharmacology |
Medium |
40446975
|