Although more difficult to detect than in the cytoplasm, it is now clear that actin polymerization occurs in the nucleus and that it plays a role in the specific processes of the nucleus such as transcription, replication, and DNA repair. A number of studies suggest that nuclear actin polymerization is promoting precise DNA repair by homologous recombination, which could potentially be of help for precise genome editing and gene therapy. This review summarizes the findings and describes the challenges and chances in the field.

Actin filaments, as key components of the cytoskeleton, have aroused great interest due to their numerous functional roles in eukaryotic cells, including intracellular electrical signaling. The aim of this research is to characterize the alternating current (AC) conduction characteristics of both globular and polymerized actin and quantitatively compare their values to those theoretically predicted earlier. Actin filaments have been demonstrated to act as conducting bionanowires, forming a signaling network capable of transmitting ionic waves in cells. We performed conductivity measurements for different concentrations of actin, considering both unpolymerized and polymerized actin to identify potential differences in their electrical properties. These measurements revealed two relevant characteristics: first, the polymerized actin, arranged in filaments, has a lower impedance than its globular counterpart; second, an increase in the actin concentration leads to higher conductivities. Furthermore, from the data collected, we developed a quantitative model to represent the electrical properties of actin in a buffer solution. We hypothesize that actin filaments can be modeled as electrical resistor-inductor-capacitor (RLC) circuits, where the resistive contribution is due to the viscous ion flows along the filaments; the inductive contribution is due to the solenoidal flows along and around the helix-shaped filament and the capacitive contribution is due to the counterion layer formed around each negatively charged filament.

Background: Chikungunya is a zoonotic disease caused by the Chikungunya virus (CHIKV), primarily transmitted to humans through infected Aedes mosquitoes. The infection is characterized by symptoms such as high fever, musculoskeletal pain, polyarthritis, and a rash, which can lead to severe complications such as encephalitis, meningitis, and even fatalities. While many disease manifestations resemble those of other viral infections, chronic arthritis caused by CHIKV is unique, and its molecular mechanisms remain ill-defined. Materials and Methods: Proteomics data from both cellular and patient levels of CHIKV infection were curated from PubMed and screened using inclusion and exclusion criteria. Patient serum proteomics data obtained from P RIDE underwent reanalysis using Proteome Discoverer 2.2. Enrichment and protein-protein interaction network analysis were conducted on differentially expressed proteins from both serum and cellular datasets. Metabolite data from CHIKV-infected patients were further retrieved, and their protein binding partners were identified using BindingDB. The protein-metabolite interaction pathway was further developed using MetaboAnalyst. Results: The proteomics data analysis revealed differential expression of proteins involved in critical host mechanisms, such as cholesterol metabolism and mRNA splicing, during CHIKV infection. Consistent upregulation of two actin cytoskeleton proteins, TAGLN2 and PFN1, was noted in both serum and cellular datasets, and their upregulations are associated with arthritis. Furthermore, alterations in purine metabolism were observed in the integrative proteome-metabolome analysis, correlating with cytoskeletal remodelling. Conclusion: Collectively, this integrative view sheds light on the involvement of actin cytoskeleton remodeling proteins and purine metabolic pathways in the development of arthritis during CHIKV infection.

Angiosarcoma is a rare refractory soft-tissue tumor with a poor prognosis and is treated by radiotherapy. The fibroblast growth factor 1 (FGF1) mutant, with enhanced thermostability due to several substituted amino acids, inhibits angiosarcoma cell metastasis, yet the mechanism of action is unclear. This study aims to clarify the FGF1 mutant mechanism of action using ISOS-1 mouse angiosarcoma cells. The wild-type FGF1 or FGF1 mutant was added to ISOS-1 cells and cultured, evaluating cell numbers over time. The invasive and migratory capacity of ISOS-1 cells was assessed by transwell analysis. ISOS-1 cell radiosensitivity was assessed by colony formation assay after X-ray irradiation. To examine whether mitogen-activated protein kinase (MEK) inhibitor counteracts the FGF1 mutant effects, a combination of MEK inhibitor and FGF1 mutant was added to ISOS-1 cells and cultured. The FGF1 mutant was observed to inhibit ISOS-1 cell proliferation, invasion and migration by sustained FGF1 signaling activation. A MEK inhibitor suppressed the FGF1 mutant-induced inhibition of proliferation, invasion and migration of ISOS-1 cells. Furthermore, the FGF1 mutant enhanced radiosensitivity of ISOS-1 cells, but MEK inhibition suppressed the increased radiosensitivity. In addition, we found that the FGF1 mutant strongly inhibits actin polymerization, suggesting that actin cytoskeletal dynamics are closely related to ISOS-1 cell radiosensitivity. Overall, this study demonstrated that in ISOS-1 cells, the FGF1 mutant inhibits proliferation, invasion and migration while enhancing radiosensitivity through sustained activation of the MEK-mediated signaling pathway.

Deoxynivalenol (DON) is one of the frequent Fusarium mycotoxins and poses a serious threat to public health worldwide. DON-induced weight loss is tightly connected with its ability to decrease feed intake by influencing gastrointestinal tract (GIT) motility. Our previous reports indicated that DON interfered with intestinal motility by injuring the contractility of enteric smooth muscle cells (SMC). Here, we further explored the potential mechanisms by employing a complementary method of transcriptomics and proteomics using the porcine enteric smooth muscle cell line (PISMC) as an experimental model. The transcriptomic and proteomic data uncover that the expression of numerous extracellular matrix (ECM) proteins and multiple integrin subunits were downregulated in PISMC under DON exposure, suppressing the ECM-integrin receptor interaction and its mediated signaling. Furthermore, DON treatment could depress actin polymerization, as reflected by the upregulated expression of Rho GTPase-activating proteins and cofilin in PISMC. Meanwhile, the expression levels of downstream contractile apparatus genes were significantly inhibited after challenge with DON. Taken together, the current results suggest that DON inhibits enteric SMC contractility by regulating the ECM-integrin-actin polymerization signaling pathway. Our findings provide novel insights into the potential mechanisms behind the DON toxicological effects in the GIT of humans and animals.

C3G is a Rap1 GEF that plays a pivotal role in platelet-mediated processes such as angiogenesis, tumor growth, and metastasis by modulating the platelet secretome. Here, we explore the mechanisms through which C3G governs platelet secretion. For this, we utilized animal models featuring either overexpression or deletion of C3G in platelets, as well as PC12 cell clones expressing C3G mutants. We found that C3G specifically regulates α-granule secretion via PKCδ, but it does not affect δ-granules or lysosomes. C3G activated RalA through a GEF-dependent mechanism, facilitating vesicle docking, while interfering with the formation of the trans-SNARE complex, thereby restricting vesicle fusion. Furthermore, C3G promotes the formation of lamellipodia during platelet spreading on specific substrates by enhancing actin polymerization via Src and Rac1-Arp2/3 pathways, but not Rap1. Consequently, C3G deletion in platelets favored kiss-and-run exocytosis. C3G also controlled granule secretion in PC12 cells, including pore formation. Additionally, C3G-deficient platelets exhibited reduced phosphatidylserine exposure, resulting in decreased thrombin generation, which along with defective actin polymerization and spreading, led to impaired clot retraction. In summary, platelet C3G plays a dual role by facilitating platelet spreading and clot retraction through the promotion of outside-in signaling while concurrently downregulating α-granule secretion by restricting granule fusion.

Actin filaments form unique structures with robust actin bundles and cytoskeletal networks affixed to the extracellular matrix and interact with neighboring cells, which are crucial structures for cancer cells to acquire a motile phenotype. This study aims to investigate a novel antitumor mechanism by which Tanshinone IIA (Tan IIA) modulates the morphology and migration of liver cancer cells via actin cytoskeleton regulation. 97H and Huh7 exhibited numerous tentacle-like protrusions that interacted with neighboring cells. Following treatment with Tan IIA, 97H and Huh7 showed a complete absence of cytoplasmic protrusion and adherens junctions, thereby effectively impeding their migration capability. The fluorescence staining of F-actin and microtubules indicated that these tentacle-like protrusions and cell-cell networks were actin-based structures that led to morphological changes after Tan IIA treatment by retracting and reorganizing beneath the membrane. Tan IIA can reverse the actin depolymerization and cell morphology alterations induced by latrunculin A. Tan IIA down-regulated actin and Rho GTPases expression significantly, as opposed to inducing Rho signaling activation. Preventing the activity of proteasomes and lysosomes had no discernible impact on the modifications in cellular structure and protein expression induced by Tan IIA. However, as demonstrated by the puromycin labeling technique, the newly synthesized proteins were significantly inhibited by Tan IIA. In conclusion, Tan IIA can induce dramatic actin cytoskeleton remodeling by inhibiting the protein synthesis of actin and Rho GTPases, resulting in the suppression of tumor growth and migration. Targeting the actin cytoskeleton of Tan IIA is a promising strategy for HCC treatment.

Nemaline myopathy (NM) is one of the most common forms of congenital myopathy and it is identified by the presence of \"nemaline bodies\" (rods) in muscle fibers by histopathological examination. The most common forms of NM are caused by mutations in the Actin Alpha 1 (ACTA1) and Nebulin (NEB) genes. Clinical features include hypotonia and muscle weakness. Unfortunately, there is no curative treatment and the pathogenetic mechanisms remain unclear. In this manuscript, we examined the pathophysiological alterations in NM using dermal fibroblasts derived from patients with mutations in ACTA1 and NEB genes. Patients\' fibroblasts were stained with rhodamine-phalloidin to analyze the polymerization of actin filaments by fluorescence microscopy. We found that patients\' fibroblasts showed incorrect actin filament polymerization compared to control fibroblasts. Actin filament polymerization defects were associated with mitochondrial dysfunction. Furthermore, we identified two mitochondrial-boosting compounds, linoleic acid (LA) and L-carnitine (LCAR), that improved the formation of actin filaments in mutant fibroblasts and corrected mitochondrial bioenergetics. Our results indicate that cellular models can be useful to study the pathophysiological mechanisms involved in NM and to find new potential therapies. Furthermore, targeting mitochondrial dysfunction with LA and LCAR can revert the pathological alterations in NM cellular models.

Herpes simplex virus type 1 (HSV-1) has been known as a common viral pathogen that can infect several parts of the body, leading to various clinical manifestations. According to this diverse manifestation, HSV-1 infection in many cell types was demonstrated. Besides the HSV-1 cell tropism, e.g., fibroblast, epithelial, mucosal cells, and neurons, HSV-1 infections can occur in human T lymphocyte cells, especially in activated T cells. In addition, several studies found that actin polymerization and filopodia formation support HSV-1 infection in diverse cell types. Hence, the goal of this review is to explore the mechanism of HSV-1 infection in various types of cells involving filopodia formation and highlight potential future directions for HSV-1 entry-related research. Moreover, this review covers several strategies for possible anti-HSV drugs focused on the entry step, offering insights into potential therapeutic interventions.

To acquire the capacity to fertilize the oocyte, mammalian spermatozoa must undergo a series of biochemical reactions in the female reproductive tract, which are collectively called capacitation. The capacitated spermatozoa subsequently interact with the oocyte zona-pellucida and undergo the acrosome reaction, which enables the penetration of the oocyte and subsequent fertilization. However, the spontaneous acrosome reaction (sAR) can occur prematurely in the sperm before reaching the oocyte cumulus oophorus, thereby jeopardizing fertilization. One of the main processes in capacitation involves actin polymerization, and the resulting F-actin is subsequently dispersed prior to the acrosome reaction. Several biochemical reactions that occur during sperm capacitation, including actin polymerization, protect sperm from sAR. In the present review, we describe the protective mechanisms that regulate sperm capacitation and prevent sAR.