Disease relevance of ARP2

• The Arp2/3 complex is implicated in actin polymerization-driven movement of Listeria monocytogenes [1].
• ARPC1/Arc40 mediates the interaction of the actin-related protein 2 and 3 complex with Wiskott-Aldrich syndrome protein family activators [2].

High impact information on ARP2

• To our knowledge, the Act2 protein from S. cerevisiae is the first highly divergent actin molecule described [3].
• The requirement of the ACT2 gene for vegetative growth of yeast cells and the existence of related genes in other eukaryotes indicate an important and conserved role for these actin-like proteins [3].
• Structural and physiological data suggest that the Act2 protein might have an important role in cytoskeletal reorganization during the cell cycle [3].
• When activated by Wiskott-Aldrich Syndrome protein (WASp), the Arp2/3 complex initiates actin filament branches from the sides of existing filaments [4].
• Animal cells control the activity of the Arp2/3 complex through the suppressor of cyclic AMP receptor (SCAR) complex to achieve cell motility [5].

Biological context of ARP2

• Disruption of the corresponding ARP2 gene leads to a terminal phenotype characterized by the presence of a single large bud [6].
• We report here the characterization of ACT2, a previously undescribed yeast split gene encoding a putative protein (391 amino acids, relative molecular mass (Mr) 44,073) that is 47% identical to yeast actin [3].
• Overall, the immunolocalization, mutant phenotypes, and genetic interaction suggest that the Arp2 protein is an essential component of the actin cytoskeleton that is involved in membrane growth and polarity, as well as in endocytosis [6].
• Temperature-sensitive arp2 mutations were created by PCR mutagenesis and selected by an ade2/SUP11 sectoring screen [6].
• The deduced amino acid sequence of Act3 is less related to conventional actins than is the deduced amino acid sequence of Act2, mainly because of three unique hydrophilic [corrected] segments [7].

Anatomical context of ARP2

• The Saccharomyces cerevisiae actin-related protein Arp2 is involved in the actin cytoskeleton [6].
• Arp2p colocalizes with mitochondria [1].
• In eukaryotic cells, the seven-protein ARP2/3 complex nucleates actin filament networks that push on the plasma membrane and organelles [8].
• Purified Arp2/3 complex binds actin filaments with a Kd of 2.3 microM and a stoichiometry of approximately one complex molecule per actin monomer [9].
• These vesicles contain the mannose 6-phosphate receptor involved in targeting proteins to the lysosome, and the actin nucleating Arp2/3 complex [10].

Associations of ARP2 with chemical compounds

• Pan1p, which binds several other endocytic proteins, is composed of multiple protein-protein interaction domains including two Eps15 Homology (EH) domains, a coiled-coil domain, an acidic Arp2/3-activating region, and a proline-rich domain [11].
• Sucrose gradient analysis of the Arp2/3 complex in the arp2-1 mutant indicated that the Arp2p and Arc18p subunits are specifically lost from the complex at restrictive temperature [12].
• NMR analysis of methyl groups at 100-500 kDa: model systems and Arp2/3 complex [13].

Physical interactions of ARP2

• Further in vivo evidence that coronin regulates the Arp2/3 complex comes from the observation that crn1 and arp2 mutants display an allele-specific synthetic interaction [14].
• Dissection of Arp2/3 complex actin nucleation mechanism and distinct roles for its nucleation-promoting factors in Saccharomyces cerevisiae [15].
• Functional interactions between the p35 subunit of the Arp2/3 complex and calmodulin in yeast [16].
• We showed previously that mutations in the Arp2/3 complex and in Bee1p/Las17p, a member of the Wiskott-Aldrich syndrome protein(WASP) family, lead to a loss of cortical actin structures (patches) in yeast [17].
• Effects of Arp2 and Arp3 nucleotide-binding pocket mutations on Arp2/3 complex function [18].

Regulatory relationships of ARP2

• BACKGROUND: WASp family proteins promote actin filament assembly by activating Arp2/3 complex and are regulated spatially and temporally to assemble specialized actin structures used in diverse cellular processes [19].
• Here we show that the yeast endocytic protein Pan1p binds to and activates the Arp2/3 complex [20].
• A two-tiered mechanism by which Cdc42 controls the localization and activation of an Arp2/3-activating motor complex in yeast [21].
• Abp1 is a multidomain protein that regulates the Arp2/3 complex and links proteins involved in endocytosis to the actin cytoskeleton [22].
• Myo1p is a weaker Arp2/3 complex activator that makes unstable branches and is enhanced by verprolin [23].

Other interactions of ARP2

• Direct regulation of Arp2/3 complex activity and function by the actin binding protein coronin [14].
• The inhibition occurs specifically in the absence of preformed actin filaments, suggesting that Crn1 may restrict Arp2/3 complex activity to the sides of filaments [14].
• Cells bearing mutations in ARP2 or ARC15 genes show decreased velocities of mitochondrial movement, loss of all directed movement and defects in mitochondrial morphology [1].
• Las17 was a much stronger activator of Arp2/3 complex than its carboxyl-terminal (WA) fragment [19].
• Genes encoding gamma-tubulin (TUB4) or any subunit of casein kinase II (CKII) suppressed this growth defect, but did not suppress the growth defect of a mutant in another subunit of the Arp2/3 complex, arp2-1 [24].

Analytical, diagnostic and therapeutic context of ARP2

• We have localized Arp2p by indirect immunofluorescence [6].
• Genetic dissection of the budding yeast Arp2/3 complex: a comparison of the in vivo and structural roles of individual subunits [25].
• Electron cryomicroscopy and three-dimensional reconstruction of Acanthamoeba castellanii and Saccharomyces cerevisiae Arp2/3 complexes bound to the WASp carboxy-terminal domain reveal asymmetric, oblate ellipsoids [4].
• Electron microscopy of Arp2/3 complex containing this Arp2 suppressor identified a structural change that also occurs upon Arp2/3 activation by nucleation promoting factors [18].
• The Arp2/3 complex, first isolated from Acanthamoeba castellani by affinity chromatography on profilin, consists of seven polypeptides; two actin-related proteins, Arp2 and Arp3; and five apparently novel proteins, p40, p35, p19, p18, and p14 (Machesky et al., 1994) [9].

References