Search Results (557)

Burn wound healing is a complex and dynamic process involving coordinated regulation of inflammation, oxidative stress, angiogenesis, and tissue remodeling. Polygonum cuspidatum, a traditional Chinese medicinal herb widely used for trauma- and inflammation-related disorders, represents an important source of bioactive compounds for tissue repair. Piceatannol (PIC), a naturally occurring stilbene constituent of P. cuspidatum, possesses potent anti-inflammatory and antioxidant activities; however, its therapeutic potential in burn wound healing remains insufficiently understood. In the present study, the therapeutic effects and underlying mechanisms of topical PIC were investigated using a murine deep second-degree burn model combined with multiple skin-related cellular models, including keratinocytes, fibroblasts, endothelial cells, and macrophages. PIC markedly accelerated wound closure and improved histological architecture, as evidenced by reduced inflammatory infiltration, enhanced collagen organization, and increased neovascularization. Mechanistically, PIC suppressed NF-κB activation and modulated KEAP1/NRF2-associated redox signaling, thereby alleviating inflammation–oxidative stress crosstalk during wound healing. In keratinocyte–fibroblast co-culture systems, PIC inhibited fibroblast-to-myofibroblast transition, reduced α-smooth muscle actin (α-SMA) expression, and attenuated excessive collagen deposition, suggesting anti-fibrotic activity. In addition, PIC promoted endothelial tube formation through activation of the STAT3–VEGF signaling axis. Collectively, these findings demonstrate that PIC facilitates burn wound repair through coordinated anti-inflammatory, antioxidative, pro-angiogenic, and anti-fibrotic effects. This study provides pharmacological support for the therapeutic potential of P. cuspidatum-derived compounds in burn management and highlights PIC as a promising candidate for topical treatment of burn injuries. Full article

Dendritic cells (DCs) are key antigen-presenting cells essential for the initiation of immune responses. Their migration is tightly regulated by adhesive structures, including podosomes and focal adhesions (FAs), allowing for interactions with the extracellular matrix (ECM) for coordinated cell movement. The organization and dynamics of these structures are controlled by actin and microtubule cytoskeletons; however, the mechanisms governing their balance in distinct DC subsets are not completely understood. In this study, we investigated cytoskeletal regulation of the interplay between podosomes and FAs in GM-CSF-derived inflammatory-like DCs (GM-BMDCs) and Flt3L-derived conventional DCs (FL-BMDCs). GM-BMDCs showed a higher capacity to form podosomes compared with FL-BMDCs, which exhibited fewer and less prominent structures. Actin depolymerization resulted in the complete loss of podosomes, whereas disruption of microtubules induced podosome reorganization and altered the structure of FAs. Importantly, cytoskeletal perturbation in both DC subsets led to podosome dissolution, highlighting the requirement of cytoskeletal integrity for their maintenance. Furthermore, actin integrity was essential for podosome-mediated ECM degradation and efficient migration of GM-BMDCs, while microtubules fine-tuned the balance between podosome and focal adhesion dynamics, thereby regulating DC motility. Full article

Discoidin domain receptor 1 (DDR1) has been implicated in fibrotic progression in multiple organs, including the kidney. However, its role in regulating cytoskeletal organization and matrix remodeling in renal fibroblasts remains unclear. Here, we investigated how DDR1 expression is regulated by profibrotic stimulation and extracellular matrix stiffness, and how DDR1 influences cytoskeletal organization and collagen remodeling. Single-cell RNA sequencing of murine kidneys subjected to unilateral ureteral obstruction (UUO) revealed enrichment of Ddr1 expression in transitional fibroblast populations during early activation. In vitro, transforming growth factor-β1 (TGF-β1) increased DDR1 expression, but DDR1 depletion did not affect canonical myofibroblast marker expression. Instead, DDR1 depletion suppressed stress fiber assembly while promoting actin-rich podosome formation associated with matrix degradation. Functionally, DDR1-deficient cells exhibited impaired focal adhesion maturation, enhanced collagen degradation, reduced gel contraction, and decreased collagen matrix stiffness as measured by atomic force microscopy. Furthermore, extracellular matrix stiffness dynamically regulated DDR1 expression, suggesting a bidirectional relationship between DDR1 expression and matrix mechanics. Together, these findings identify DDR1 as a modulator of cytoskeletal remodeling that governs the balance between matrix-degradation and contractile remodeling programs in renal fibroblasts. Full article

Neurons achieve their highly polarized architecture by coordinating cytoskeletal systems across space and time, enabling axons to extend over remarkable distances and dendrites to elaborate complex arbours. Early neuroanatomists described intracellular “neurofibrils,” yet these structures remained poorly understood until electron microscopy resolved them into three distinct polymer systems: microtubules, actin filaments, and intermediate filaments. Although this framework clarified neuronal ultrastructure, it simultaneously established a conceptual hierarchy in which microtubules and actin were regarded as the principal drivers of neurite growth, while intermediate filaments were relegated to a passive, supportive role. Unlike prior reviews that document vimentin dynamics primarily from a cell-biological standpoint, this review integrates historical, conceptual, and epistemological perspectives to examine both how and why that hierarchy arose and how it has been dismantled. This review traces how that hierarchy arose and why it has been increasingly reconsidered in favour of intermediate filaments, focusing on vimentin as a case study. Evidence from live cell imaging, molecular manipulation, and genetic models shows that vimentin is dynamically regulated rather than static. Vimentin networks remodel continuously, exchange subunits with soluble pools, and move in coordination with microtubules. Most recently, sparse single-filament labelling combined with correlative volume electron microscopy has demonstrated that individual vimentin filaments remain motile even within dense perinuclear networks previously assumed to be static, a finding that fundamentally redefines what filament density implies about cytoskeletal organization. In neural and neural precursor cells, vimentin expression is developmentally regulated and is prominent during early differentiation stages associated with neurite initiation giving way to neurofilaments in mature neurons. Functional studies further link vimentin to neurite formation and extension, cytoskeletal coordination, organelle positioning, and cellular stress responses. Philosophical analysis reveals that these empirical advances were inseparable from shifts in imaging technology and conceptual framing, and that epistemic risks including model dependency and confirmation bias can be mitigated through methodological pluralism and explicit model disclosure. Taken together, these findings support a revised understanding of intermediate filaments as active, context-dependent contributors to neuronal development and plasticity, and illustrate the value of integrating biological evidence with historical and philosophical reflection. Full article

Tropomyosins (Tpm) are the family of actin-binding proteins encoded by four genes in humans. Missense mutations in the TPM1 gene associated with cardiomyopathies have been studied in the sarcomeric isoform Tpm1.1. The cardiomyopathy-causing mutations E40K and E54K are located in exon 2b of the TPM1 gene and may be expressed in non-muscle cytoplasmic Tpm isoforms, including Tpm1.7, which is associated with early tissue development. In the present work, we investigate the effects of mutations E40K and E54K on the properties of Tpm1.7. The E40K and E54K mutations caused destabilization of the Tpm1.7 molecule at the N- and C-termini parts. Neither mutation affected the Tpm1.7 affinity for filamentous actin (F-actin). The bending stiffness of F-actin/Tpm1.7 E40K filaments was lower compared to F-actin/Tpm1.7 WT (wild-type). The interplay of Tpm1.7 and motor proteins was studied in an in vitro motility assay with skeletal myosin. Tpm1.7 WT reduced the sliding velocity of F-actin by half; the velocity of F-actin with Tpm1.7 E54K did not differ from that of bare F-actin; and Tpm1.7 E40K decreased the F-actin velocity by approximately threefold. While Tpm1.7 E40K did not affect the protective effect of Tpm1.7 against F-actin severing by cofilin-1, the E54K mutation enhanced protection against cofilin-1. Thus, cardiomyopathic mutations in the TPM1 gene can affect the properties of non-muscle Tpm isoforms, which indicates that this should be taken into account when studying the molecular mechanisms of the pathogenesis of these diseases. Full article

Actin Depolymerizing Factor (ADF) proteins are key regulators of actin cytoskeleton dynamics, mediating numerous essential plant life processes, including cell elongation, division, and signal transduction in response to environmental stress. Although ADF functions are well characterized in herbaceous plants, systematic analysis of poplar ADFs and their roles in osmotic stress response remains largely unexplored. In this study, we identified 14 PtADF genes in the Populus trichocarpa genome, mapped across ten distinct chromosomes. Phylogenetic analysis categorized all the ADFs into seven groups, with PtADFs displaying conserved motifs. PtADF gene family expansion was primarily attributed to whole-genome duplication (WGD) events. Evolutionary constraint analysis, evidenced by a Ka/Ks ratio < 1, indicated significant selective pressure on these genes. Promoter regions of PtADF genes were enriched with cis-acting elements responsive to hormones and stresses. Transcriptome profiling showed that five PtADF genes were significantly induced under drought stress. We then identified the homologous genes of PtADFs in P. euphratica, a Populus species with superior environmental stress adaptability, and qRT-PCR analysis revealed that four homologous PeADFs were significantly induced by mannitol treatment. These results characterize the basic features of the PtADF gene family and provide a general reference for screening candidate PeADF genes for further research in poplar. Full article

Talaromyces marneffei is a dimorphic fungal pathogen that can subvert host immune defenses; however, the molecular mechanisms underlying its interactions with host cells remain incompletely understood. Glutathione peroxidase from T. marneffei (TmGpx1) has previously been identified as an antigenic protein that elicits antibody responses in patients with talaromycosis. To elucidate the contribution of TmGpx1 during human–fungal pathogen interaction, the yeast two-hybrid system was performed using TmGpx1 as bait to screen a cDNA library derived from non-induced human macrophage cells. Sixteen candidate host protein partners were identified, with Gene Ontology analysis revealing their predominant association with cytoskeletal and extracellular exosome components. To examine the atomic-level structural interface and dynamic behavior of protein–protein interactions, we employed molecular dynamics (MD) simulations to investigate the interaction between TmGpx1 and FKBP15, a human protein involved in early endosomal regulation and associated with both microtubule and actin filaments. Per-residue decomposition analysis using gmx_MMPBSA identified LEU124 of TmGpx1 and ARG616 of FKBP15 as critical residues mediating the protein–protein interaction. Notably, the key residues of TmGpx1 are located toward the N-terminus and are mapped outside of the catalytic active site, suggesting that the interaction of TmGpx1 with host cytoskeletal components may occur independently of its enzymatic antioxidant activity. Overall, our findings provide novel insights into the repertoire of host cytoskeletal and membrane trafficking proteins that may be targeted for remodeling during T. marneffei infection. Elucidation of these molecular interactions advances our understanding of host–pathogen dynamics and opens new avenues for the development of targeted diagnostics and therapeutic strategies against talaromycosis. Full article

Enhancing crop stress tolerance to ensure global food security is one of the core challenges in agricultural science. Plants predominantly face biotic and abiotic stresses, to which they respond by activating finely regulated signal perception and transduction pathways, thereby improving their survival in adverse environments. The plant cytoskeleton, composed of microtubules and actin filaments, plays a pivotal role in this adaptive process. It functions both as a hub for integrating external stress signals and as a key regulator of downstream signaling and cellular responses. Upon stress, the cytoskeleton undergoes dynamic remodeling, a process driven mainly by microtubule-associated proteins (MAPs) and actin-binding proteins (ABPs). This review systematically summarizes current knowledge on cytoskeletal remodeling in plants under environmental stress, particularly focusing on the functions and mechanisms of MAPs and ABPs in cytoskeletal remodeling. Furthermore, it outlines the regulatory network through which the plant cytoskeleton orchestrates stress adaptation. Full article

Chemotaxis enables eukaryotic cells to detect and migrate along extracellular chemoattractant gradients spanning several orders of magnitude. This remarkable dynamic range relies on adaptation, a process that allows cells to reset their signaling machinery while preserving sensitivity to incremental changes in stimulus intensity. Although numerous actin-dependent feedback mechanisms have been characterized, the molecular basis of adaptation within an actin-independent core gradient-sensing module remains poorly understood. Here, we identify the Ras GTPase-activating protein, C2GAP1, as a critical F-actin-independent effector of the heterotrimeric G protein, Gα2, in Dictyostelium discoideum. Using cytoskeleton-free gradient-sensing cells, quantitative imaging, biochemical assays, FRET-based G-protein activation measurements, and structural modeling, we demonstrate that C2GAP1 controls concentration-dependent adaptation during gradient sensing. Mechanistically, C2GAP1 directly associates with Gα2 in both GDP- and GTP-bound states, with preferential binding to activated Gα2, thereby sustaining membrane recruitment and locally attenuating Ras and downstream signaling. Loss of C2GAP1 enhances G-protein activation, disrupts local inhibition, and impairs rapid reorientation in dynamic gradients. These findings define a direct coupling between heterotrimeric G proteins and the RasGAP, C2GAP1, as a core adaptive module that enables gradient sensing across a wide concentration range. Full article

Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin receptor kinase B (TrkB) are classically associated with neuroplasticity, but increasing evidence suggests a broader role for BDNF/TrkB signaling in systemic stress adaptation beyond the central nervous system. Strenuous exercise is a model of functional stress that may become a clinically relevant renal challenge under conditions such as dehydration, heat stress, vascular vulnerability, and repeated exposure. Neuroendocrine stress activation, hemodynamic perturbations, and cytoskeletal instability are key factors that may contribute to glomerular barrier dysfunction in this setting. BDNF biogenesis is complex, and circulating BDNF largely reflects platelet-associated pools and context-dependent release. At the tissue level, BDNF/TrkB signaling can activate actin-regulatory pathways involved in cellular resilience. The podocyte is of particular interest because its actin-dependent architecture functionally parallels that of neurons and is essential for maintenance of the glomerular filtration barrier. Within this framework, BDNF/TrkB signaling may stabilize podocyte actin dynamics, reduce foot process effacement, and attenuate proteinuria. The present review focuses on the brain–kidney axis and the potential renoprotective role of BDNF/TrkB signaling, while highlighting major knowledge gaps regarding BDNF availability to glomerular cells, isoform-specific TrkB actions, and causal inference in humans exposed to repeated exercise-related renal stress. However, current human evidence is insufficient to define the dominant source and delivery route of BDNF to glomerular cells during exercise-related renal stress. Therefore, BDNF/TrkB is discussed here as a candidate modulatory/resilience pathway rather than an established causal driver. Full article

The deficiency of TCOF1 is closely associated with multiple cellular dysfunctions, but its function in mitochondrial homeostasis and cytoskeletal regulation remains unclear. First, our research revealed that TCOF1 deficiency significantly inhibits tumor cell migration, suggesting TCOF1 plays a crucial role in cellular motility. Further studies demonstrated that TCOF1 deficiency disrupts normal F-actin polymerization, compromises cytoskeletal structural integrity, and impairs the dynamic assembly of F-actin, thereby affecting cell morphology and motility functions. Additionally, TCOF1 deficiency leads to mitochondrial dysfunction characterized by aberrant energy metabolism. Mechanistically, TCOF1 deficiency decreased the protein levels of p53, subsequently affecting mitochondrial biogenesis and functional maintenance, suggesting TCOF1 may regulate mitochondrial homeostasis via a p53-dependent pathway. Collectively, our study reveals TCOF1’s role in regulating tumor cell migration by influencing F-actin assembly and the p53-mitochondrial axis, playing a critical role in maintaining cytoskeletal dynamics and energy metabolism. Full article

Titanium and its alloys are widely used for orthopedic implants, but their intrinsic bioinertness may hinder osseointegration. In this study, titanium dioxide nanotube (TNT) arrays were fabricated on Ti-6Al-4V scaffolds via anodization, and their effects on the adhesion behavior of human bone marrow mesenchymal stem cells (hBMSCs) were investigated. Surface characterization showed that anodization successfully generated ordered TNT layers, increased surface roughness, enhanced protein adsorption, and induced an apparent superhydrophilic wetting response. Compared to the untreated scaffold and TNT50, the small-diameter TNT10 surface significantly promoted hBMSC adhesion and proliferation. Microscope imaging further revealed enhanced cell spreading, F-actin organization, and vinculin expression on TNT surfaces, with the most prominent focal adhesion-related staining observed in TNT10. Quantitative proteomic analysis showed that TNT10 was associated with coordinated remodeling of adhesion- and cytoskeleton-related molecular programs, including focal adhesion, cell–substrate junction, and regulation of the actin cytoskeleton. In contrast, TNT50, despite supporting obvious cytoskeletal remodeling, was more compatible with a dynamic, higher-turnover adhesion state. Overall, these findings suggest that small-diameter TNTs provide a more favorable interfacial microenvironment for stable early hBMSC adhesion on porous titanium scaffolds. Full article

The lateral organization of the plasma membrane (PM) is vital for cellular signaling, yet the specific mechanisms by which the internal cortical actin meshwork templates the organization of the external lipid leaflet remain poorly understood. While established models like the ‘picket-fence’ emphasize physical barriers to diffusion, recent observations of fiber-like “ghost” structures in the distribution of glycosylphosphatidylinositol-anchored proteins (GPI-APs) suggest a more intricate mode of spatial coordination. In this study, we utilize imaging total internal reflection fluorescence correlation spectroscopy (ITIR-FCS) and variable-angle TIRF to resolve whether these filamentous patterns represent genuine membrane-proximal features or optical artifacts of cytosolic transport. Our results demonstrate that these fiber-like tracks are strictly confined to the immediate PM interface and disappear as the evanescent field probes deeper into the cytosol. While the spatial distribution of GPI-APs is templated by the underlying actin meshwork, quantitative diffusion mapping shows that the lateral dynamics of the probe remains largely uniform and is not significantly modulated by these filamentous patterns. By pharmacologically perturbing the actin scaffold and membrane cholesterol, we show that this transbilayer coupling is contingent upon a cholesterol-dependent cytoskeletal pinning mechanism. These findings demonstrate a decoupling of spatial organization and molecular dynamics, providing evidence for how the actin scaffold patterns nanoscale membrane organization without imposing long-range barriers to diffusion. Full article

Background/Objectives: Diabetic small fiber neuropathy and related sensory and epidermal problems affect up to 70% of all patients with diabetes. Long-term hyperglycemia disrupts cytoskeletal organization and axonal transport; however, molecular changes within human diabetic epidermis remain understudied. Diaph1 and its cytoskeletal ligands, including β-Actin and Profilin, are key regulators of cytoskeletal dynamics and may be associated with diabetes-related alterations in skin structure and innervation. Methods: Sixteen patients with type 2 diabetes, aged 43.3 ± 9.6 years (disease duration 18.9 ± 8.7 years), and twelve non-diabetic controls, aged 43.9 ± 8.9 years, were enrolled in the study. All participants provided informed consent. Skin punch biopsies were obtained under local anesthesia and processed for staining of PGP 9.5, Diaph1, β-Actin, and Profilin. Quantitative image analysis was performed to assess stained area fraction, signal intensity, and intraepidermal nerve fiber density. Statistical comparisons and Spearman’s rank correlation analyses were used to evaluate group differences and associations between staining parameters. Results: Diabetic skin samples exhibited a significant reduction in PGP 9.5-positive intraepidermal nerve fibers, indicating reduced cutaneous innervation. In contrast, Diaph1 and Profilin showed broader and more diffuse epidermal staining, while β-Actin displayed altered staining patterns and intensity. Significant correlations between Diaph1- and β-Actin-related staining measures indicated an association consistent with altered cytoskeletal organization under chronic hyperglycemic conditions. Conclusions: Long-standing type 2 diabetes was associated with reduced PGP 9.5-positive intraepidermal nerve fibers, together with altered epidermal staining patterns of Diaph1, Profilin and β-Actin. These findings indicate coexisting cutaneous denervation and cytoskeletal alterations in diabetic skin. Full article

Actin is a key component of the cytoskeleton and plays diverse roles in cellular processes. Autophagy regulates homeostasis through various mechanisms that recycle nutrients and degrade unnecessary or harmful cellular components and aggregates. These two processes are engaged in a highly conserved crosstalk through which they regulate each other, including autophagolysosomal formation and regulation of actin dynamics. The regulation of autophagy is involved in cancer, neurodegeneration, infectious diseases, and inflammation, providing possible avenues for treatments for these diseases. In this review, we summarize current knowledge of the actin–autophagy interplay and regulation, and explore the possible implications for disease progression and therapies. Although more research is necessary to strengthen the effectiveness of therapies that target the regulation of autophagy and actin dynamics, significant strides have already been made, clearly indicating the potential benefit of targeting these processes. Full article