Cytoskeletal network dysregulation is a pivotal determinant in various immunodeficiencies and autoinflammatory conditions. This report reviews the significance of actin remodeling in disease pathogenesis, focusing on the Arp2/3 complex and its regulatory subunit actin related protein 2/3 complex subunit 1B (ARPC1B). A spectrum of cellular dysfunctions associated with ARPC1B deficiency, impacting diverse immune cell types, is elucidated. The study presents a patient featuring recurrent and persistent eosinophilia attributed to homozygous ARPC1B mutation alongside concomitant compound heterozygous cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. We used ARPC1B antibody to stain the patient's peripheral blood lymphocytes and those of the control. The defect in the ARPC1B gene in the present patient caused absent/low expression by immunofluorescence microscopy. The intricate interplay between cytoskeletal defects and immunological manifestations underscores the complexity of disease phenotypes, warranting further exploration for targeted therapeutic strategies.
Humans ; Actin-Related Protein 2-3 Complex/genetics* ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Eosinophilia/genetics* ; Homozygote ; Mutation ; Recurrence

The baculovirus-induced actin polymerization is mainly associated with the virus nucleocapsid protein P78/83, which is homologous with WASP proteins that can activate Arp2/3 complex and induce the actin polymerization. In order to explore the role of Arp2/3 complex in the baculovirus replication, the P40 subunit of Arp2/3 complex from Sf9 (Spodoptera frugiperda 9) cell line was cloned and characterized. Immunofluorescent microscopy assay indicated that P40 was recruited to the inner-side of nuclear membrane during virus infection, which was in accordance with nuclear F-actin distribution in virus-infected cells as documented in our previous research, suggesting P40 could be used to track Arp2/3 complex subcellular distribution changes during virus infection. In addition, co-immunoprecipitation assay demonstrated that P40 interacted with P78/83 only in virus-infected cells, suggesting that actin polymerization induced by P78/83-Arp2/3 complex during baculovirus infection was regulated by some unidentified virus factors.
Actin-Related Protein 2-3 Complex ; chemistry ; genetics ; metabolism ; Amino Acid Sequence ; Animals ; Capsid Proteins ; genetics ; metabolism ; Cell Line ; Cloning, Molecular ; Humans ; Insect Proteins ; chemistry ; genetics ; metabolism ; Molecular Sequence Data ; Nucleopolyhedrovirus ; genetics ; metabolism ; Phylogeny ; Protein Binding ; Sequence Alignment ; Sf9 Cells ; Spodoptera ; chemistry ; genetics ; metabolism ; virology

Cellular senescence is a tumor-suppressive process instigated by proliferation in the absence of telomere replication, by cellular stresses such as oncogene activation, or by activation of the tumor suppressor proteins, such as Rb or p53. This process is characterized by an irreversible cell cycle exit, a unique morphology, and expression of senescence-associated-beta-galactosidase (SA-beta-gal). Despite the potential biological importance of cellular senescence, little is known of the mechanisms leading to the senescent phenotype. p41-Arc has been known to be a putative regulatory component of the mammalian Arp2/3 complex, which is required for the formation of branched networks of actin filaments at the cell cortex. In this study, we demonstrate that p41-Arc can induce senescent phenotypes when it is overexpressed in human tumor cell line, SaOs-2, which is deficient in p53 and Rb tumor suppressor genes, implying that p41 can induce senescence in a p53-independent way. p41-Arc overexpression causes a change in actin filaments, accumulating actin filaments in nuclei. Therefore, these results imply that a change in actin filament can trigger an intrinsic senescence program in the absence of p53 and Rb tumor suppressor genes.
Actin Cytoskeleton/metabolism ; Actin-Related Protein 2-3 Complex/*metabolism ; *Cell Aging ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Fibroblasts/physiology ; Humans ; Recombinant Proteins/genetics/*metabolism ; Retinoblastoma Protein/*deficiency/genetics ; Tumor Suppressor Protein p53/*deficiency/genetics