Arp 2/3 complex

NPC intracellular cholesterol transporter 1 (NPC1) is a multipass, transmembrane glycoprotein mostly recognized for its key role in facilitating cholesterol efflux. Mutations in the NPC1 gene result in Niemann-Pick disease, type C (NPC), a fatal, lysosomal storage disease. Due to the progressively expanding implications of NPC1-related disorders, we investigated endogenous NPC1 protein-protein interactions in the mouse cortex and human-derived iPSCs neuronal models of the disease through coimmunoprecipitation-coupled with LC-MS based proteomics...

Arp2/3 complex nucleates branched actin filaments for cell and organelle movements. Here we report a 2.7 Å resolution cryo-EM structure of the mature branch junction formed by S. pombe Arp2/3 complex that provides details about interactions with both mother and daughter filaments. We determine a second structure at 3.2 Å resolution with the phosphate analog BeFx bound with ADP to Arp3 and ATP bound to Arp2. In this ADP-BeFx transition state the outer domain of Arp3 is rotated 2° toward the mother filament compared with the ADP state and makes slightly broader contacts with actin in both the mother and daughter filaments...

Actin cytoskeleton remodeling sustains the ability of cytotoxic T cells to search for target cells and eliminate them. We here investigated the relationship between energetic status, actin remodeling, and functional fitness in human CD8+ effector T cells. Cell spreading during migration or immunological synapse assembly mirrored cytotoxic activity. Morphological and functional fitness were boosted by interleukin-2 (IL-2), which also stimulated the transcription of glycolytic enzymes, actin isoforms, and actin-related protein (ARP)2/3 complex subunits...

Coordination of filament assembly and membrane remodeling is required for the directional migration of cancer cells. The Wiskott-Aldrich syndrome protein (WASp) recruits the actin-related protein (Arp) 2/3 complex to assemble branched actin networks. The goal of our study was to assess the potential regulatory role exerted by the novel long non-coding RNA (lncRNA) LINC00869 on hepatocellular carcinoma (HCC) cells. We used HCC cells to overexpress or knockdown LINC00869, analyzed patient data from publicly available databases and Cancer Hospital Affiliated with Zhengzhou University, and used a xenograft mouse model of HCC to study the molecular mechanism associated with LINC00869 expression...

Arp2/3 complex generates branched actin networks that drive fundamental processes such as cell motility and cytokinesis. The complex comprises seven proteins, including actin-related proteins (Arps) 2 and 3 and five scaffolding proteins (ArpC1-ArpC5) that mediate interactions with a pre-existing (mother) actin filament at the branch junction. Arp2/3 complex exists in two main conformations, inactive with the Arps interacting end-to-end and active with the Arps interacting side-by-side like subunits of the short-pitch helix of the actin filament...

The paper presents the result of assessing the antiradical status of consumers (in the context of Russia) in connection with their well-being. This approach is based on a multistage study, in which the results of sociological surveys were applied, as well as estimates of the antiradical potential (ARP) of diets obtained using neural networks, bootstrapping the chemical composition of diets, and calculating reference values using mathematical models. The paper presents data collected from residents living in the territories of at least 21 regions and cities of Russia: Magadan, Saint Petersburg, Moscow, Krasnodar, Lipetsk, Vladivostok, Novosibirsk, Omsk, Voronezh, etc...

BACKGROUND: Hyperglycemia-induced accumulation of reactive oxygen species (ROS) is a major risk factor for diabetic retinopathy (DR). Sarsasapogenin is a natural steroidal saponin that is known to have excellent antidiabetic effects and improve diabetic complications, but its potential efficacy and mechanism for DR are unknown. OBJECTIVES: The current study was designed to explore whether sarsasapogenin inhibits hyperglycemia-induced oxidative stress in human retinal pigment epithelial (RPE) ARPE-19 cells and to elucidate the molecular mechanisms...

Eukaryotic cell migration requires continuous supply of actin polymers at the leading edges to make and extend lamellipodia or pseudopodia. Linear and branched filamentous actin polymers fuel cell migration. Branching of actin polymers in the lamellipodia/pseudopodia is facilitated by the actin-related protein (Arp) 2/3 complex, whose function is essentially controlled by the Scar/WAVE complex. In cells, the Scar/WAVE complex remains inactive, and its activation is a highly regulated and complex process. In response to signalling cues, GTP-bound Rac1 associates with Scar/WAVE and causes activation of the complex...

Current treatment options for organic waste contaminated with per- and polyfluoroalkyl substances (PFAS) are generally limited to incineration, composting or landfilling, all resulting in emissions. Dry pyrolysis is a promising emerging alternative to these practices, but there is uncertainty related to the fate of PFAS during this process. The present work first developed a robust method for the determination of PFAS in complex matrices, such as sewage sludge and biochar. Then, a mass balance was established for 56 different PFAS during full-scale pyrolysis (2-10 kg biochar hr-1 , 500-800 °C) of sewage sludges, food waste reject, garden waste and waste timber...

Cr(VI) is difficult to remove from wastewater via a one-step method because it is a type of oxyanion. Developing ARPs to selectively remove total Cr is critical for Cr(VI) remediation, including Cr(VI) adsorption-reduction and Cr(III) complexation. Hereon, chitosan and biochar modified-FeS (CTS-FeS@BC) was prepared to apply in the selective removal of total Cr from wastewaters. The results showed that the activity of amorphous FeS on CTS-FeS@BC for Cr(VI) removal (110.0 mg/g FeS) was significantly enhanced by CTS and BC, and efficiency was inhibited slightly by many anions and humic acid (HA)...

Macroendocytosis comprising phagocytosis and macropinocytosis is an actin-driven process regulated by small GTPases that depend on the dynamic reorganization of the membrane that protrudes and internalizes extracellular material by cup-shaped structures. To effectively capture, enwrap, and internalize their targets, these cups are arranged into a peripheral ring or ruffle of protruding actin sheets emerging from an actin-rich, nonprotrusive zone at its base. Despite extensive knowledge of the mechanism driving actin assembly of the branched network at the protrusive cup edge, which is initiated by the actin-related protein (Arp) 2/3 complex downstream of Rac signaling, our understanding of actin assembly in the base is still incomplete...

Improving the chemotherapy sensitivity of bladder cancer is a current clinical challenge. It is critical to seek out effective combination therapies that include low doses of cisplatin due to its dose-limiting toxicity. This study aims to investigate the cytotoxic effects of the combination therapy including proTAME, a small molecule inhibitor, targeting Cdc-20 and to determine the expression levels of several APC/C pathway-related genes that may play a role in the chemotherapy response of RT-4 (bladder cancer) and ARPE-19 (normal epithelial) cells...

The β-substituted porphyrinoids commonly used to form functional assembled systems in nature yet are still scarcely used in material chemistry probably due to the laborious synthesis of these compounds. In this work, β-octa[(4-diethoxyphosphoryl)phenyl]porphyrin ( 2HOPPP ) and its metal (Zn(II), Cd(II), Cu(II), and Ni(II)) complexes were prepared in good yields. These highly soluble chromophores were characterized in solution using spectroscopic (NMR, UV-vis, fluorescence), electrochemical, and spectroelectrochemical methods...

The aim of this study was to improve the solubility of aripiprazole (ARP) by fabricating binary and ternary inclusion complexes with methyl-β-cyclodextrin (MβCD) and L-Arginine (LA). Physical mixing and lyophilization were used in the following molar ratios: 1:1, 1:2.5, 1:4, 1:9, 1:1:1, 1:1:0.27, 1:4:1, 1:9:1, 1:3.6:3.6. The developed formulations were analyzed by solubility and dissolution. They were characterized by FTIR, XRD, DSC, SEM and TGA. Ternary formulations prepared by the lyophilization method showed improved dissolution rates in simulated gastric fluid (SGF)...

BACKGROUND: Intratumoral heterogeneity is the primary challenge in the treatment of glioblastoma (GBM). The presence of glioma stem cells (GSCs) and their conversion between different molecular phenotypes contribute to the complexity of heterogeneity, culminating in preferential resistance to radiotherapy. ARP2/3 (actin-related protein-2/3) complexes (ARPs) are associated with cancer migration, invasion and differentiation, while the implications of ARPs in the phenotype and resistance to radiotherapy of GSCs remain unclear...

In plants, the actin cytoskeleton plays a critical role in defense against diverse pathogens. The formation of actin patches is essential for the intracellular transport of organelles and molecules toward pathogen penetration sites and the formation of papillae for an early cellular response to powdery mildew attack in Arabidopsis thaliana . This response process is regulated by the actin-related protein (ARP)2/3 complex and its activator, the WAVE/SCAR complex (W/SRC). The ARP2/3 complex is also required for maintaining steady-state levels of the defense-associated protein, PENETRATION 1 (PEN1), at the plasma membrane and for its deposition into papillae...

Purpose: This study aimed to explore whether RO4929097 (RO), a specific γ-secretase inhibitor, could inhibit the subretinal fibrosis in laser-induced mouse model and the relevant molecular mechanisms. Methods: Male C57BL/6J mice were used to produce choroidal neovascularization (CNV) and subretinal fibrosis by laser photocoagulation, and RO was administered intravitreally 1 day after laser induction. The sizes of CNV and subretinal fibrosis were measured and quantified in both 2D and 3D constructions...

Aim: Chronic inflammation is crucial for age-related macular degeneration (AMD) pathogenesis. However, the mechanism involved in activating inflammation remains unclear. This study is aimed at investigating whether nuclear factor erythrocyte-associated factor 2 (Nrf2) negatively regulated the Nod-like receptor protein 3 (NLRP3) inflammasomes through the thioredoxin 1 (Trx1)/thioredoxin interaction protein (TXNIP) complex. Methods: We determined the optimal hydrogen peroxide (H2 O2 ) concentration, time, and changes in reactive oxygen species (ROS) levels...

(1) The serine protease inhibitor Kazal type 1 (SPINK1) inhibits trypsin activity in zymogen granules of pancreatic acinar cells. Several mutations in the SPINK1 gene are associated with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). The most common variant is SPINK1 p.N34S. Although this mutation was identified two decades ago, the mechanism of action has remained elusive. (2) SPINK1 and human cationic trypsin (TRY1) were expressed in E. coli , and inhibitory activities were determined. Crystals of SPINK1-TRY1 complexes were grown by using the hanging-drop method, and phases were solved by molecular replacement...

We present STM/STS, ARPES and magnetotransport studies of the surface topography and electronic structure of pristine Bi2 Se3 in comparison to Bi1.96 Mg0.04 Se3 and Bi1.98 Fe0.02 Se3 . The topography images reveal a large number of complex, triangle-shaped defects at the surface. The local electronic structure of both the defected and non-defected regions is examined by STS. The defect-related states shift together with the Dirac point observed in the undefected area, suggesting that the local electronic structure at the defects is influenced by doping in the same way as the electronic structure of the undefected surface...