Motor-driven marginal band coiling promotes cell shape change during platelet activation
Ontology highlight
ABSTRACT:
SUBMITTER: Boubou Diagouraga
PROVIDER: S-JCBD-201306085 | bioimages |
REPOSITORIES: bioimages
Similar Datasets
Project description:Platelets float in the blood as discoid particles. Their shape is maintained by microtubules organized in a ring structure, the so-called marginal band (MB), in the periphery of resting platelets. Platelets are activated after vessel injury and undergo a major shape change known as disc to sphere transition. It has been suggested that actomyosin tension induces the contraction of the MB to a smaller ring. In this paper, we show that antagonistic microtubule motors keep the MB in its resting state. During platelet activation, dynein slides microtubules apart, leading to MB extension rather than contraction. The MB then starts to coil, thereby inducing the spherical shape of activating platelets. Newly polymerizing microtubules within the coiled MB will then take a new path to form the smaller microtubule ring, in concerted action with actomyosin tension. These results present a new view of the platelet activation mechanism and reveal principal mechanistic features underlying cellular shape changes.
| S-EPMC3897189 | biostudies-literature
Project description:Current theories suggest that an error-driven learning process updates trial-by-trial to facilitate motor adaptation. How this process interacts with motor cortical preparatory activity-which current models suggest plays a critical role in movement initiation-remains unknown. Here, we evaluated the role of motor preparation during visuomotor adaptation. We found that preparation time was inversely correlated to variance of errors on current trials and mean error on subsequent trials. We also found causal evidence that intracortical microstimulation during motor preparation was sufficient to disrupt learning. Surprisingly, stimulation did not affect current trials, but instead disrupted the update computation of a learning process, thereby affecting subsequent trials. This is consistent with a Bayesian estimation framework where the motor system reduces its learning rate by virtue of lowering error sensitivity when faced with uncertainty. This interaction between motor preparation and the error-driven learning system may facilitate new probes into mechanisms underlying trial-by-trial adaptation.
| S-EPMC7185427 | biostudies-literature
Project description:Transforming growth factor-beta (TGFβ) is a potent immunosuppressive cytokine that inhibits the anti-tumor responses of NK cells and T cells. However, the stimulation of natural killer (NK) cells with pro-inflammatory cytokines decreases NK cell sensitivity to TGFβ. Herein, we sought to determine if TGFβ imprinting (TGFβi) during NK cell activation and expansion would decrease NK cell sensitivity to TGFβ suppression. To this end, we demonstrate that the activation of NK cells during chronic IL-2 stimulation and TGFβi potently induces NK cell hypersecretion of interferon-gamma (IFNγ) and tumor necrosis factor-alpha (TNFα) in response to tumor targets which persists for at least one month in vitro after the removal of TGFβ. TGFβi NK cell cytokine hypersecretion is induced following both cytokine and tumor activation. Further, TGFβi NK cells have a marked suppression of SMAD3 and T-bet which is associated with altered chromatin accessibility. In contrast to their heightened cytokine secretion, TGFβi NK cells downregulate several activating receptors, granzyme and perforin, and upregulate TRAIL, leading to cell-line-specific alterations in cytotoxicity. These findings may impact our understanding of how TGFβ affects NK cell development and anti-tumor function.
| S-EPMC6267005 | biostudies-literature
Project description:Size homeostasis is fundamental in cell biology, but it is not clear how large cells such as neurons can assess their own size or length. We examined a role for molecular motors in intracellular length sensing.Computational simulations suggest that spatial information can be encoded by the frequency of an oscillating retrograde signal arising from a composite negative feedback loop between bidirectional motor-dependent signals. The model predicts that decreasing either or both anterograde or retrograde signals should increase cell length, and this prediction was confirmed upon application of siRNAs for specific kinesin and/or dynein heavy chains in adult sensory neurons. Heterozygous dynein heavy chain 1 mutant sensory neurons also exhibited increased lengths both in vitro and during embryonic development.Moreover, similar length increases were observed in mouse embryonic fibroblasts upon partial downregulation of dynein heavy chain 1.Thus, molecular motors critically influence cell length sensing and growth control.
| S-EPMC3389498 | biostudies-literature
Project description:Activation of immune cells relies on a dynamic actin cytoskeleton. Despite detailed knowledge of molecular actin assembly, the exact processes governing actin organization during activation remain elusive. Using advanced microscopy, we here show that Rat Basophilic Leukemia (RBL) cells, a model mast cell line, employ an orchestrated series of reorganization events within the cortical actin network during activation. In response to IgE antigen-stimulation of FCε receptors (FCεR) at the RBL cell surface, we observed symmetry breaking of the F-actin network and subsequent rapid disassembly of the actin cortex. This was followed by a reassembly process that may be driven by the coordinated transformation of distinct nanoscale F-actin architectures, reminiscent of self-organizing actin patterns. Actin patterns co-localized with zones of Arp2/3 nucleation, while network reassembly was accompanied by myosin-II activity. Strikingly, cortical actin disassembly coincided with zones of granule secretion, suggesting that cytoskeletal actin patterns contribute to orchestrate RBL cell activation.
| S-EPMC6405992 | biostudies-literature
Project description:Motor-activity-related mental tasks are widely adopted for brain-computer interfaces (BCIs) as they are a natural extension of movement intention, requiring no training to evoke brain activity. The ideal BCI aims to eliminate neuromuscular movement, making motor imagery tasks, or imagined actions with no muscle movement, good candidates. This study explores cortical activation differences between motor imagery and motor execution for both upper and lower limbs using functional near-infrared spectroscopy (fNIRS). Four simple finger- or toe-tapping tasks (left hand, right hand, left foot, and right foot) were performed with both motor imagery and motor execution and compared to resting state. Significant activation was found during all four motor imagery tasks, indicating that they can be detected via fNIRS. Motor execution produced higher activation levels, a faster response, and a different spatial distribution compared to motor imagery, which should be taken into account when designing an imagery-based BCI. When comparing left versus right, upper limb tasks are the most clearly distinguishable, particularly during motor execution. Left and right lower limb activation patterns were found to be highly similar during both imagery and execution, indicating that higher resolution imaging, advanced signal processing, or improved subject training may be required to reliably distinguish them.
| S-EPMC5435907 | biostudies-literature
Project description:BackgroundGlioma stem cells (GSCs) are responsible for glioma recurrence and drug resistance, yet the mechanisms underlying their maintenance remains unclear. This study aimed to identify enhancer-controlled genes involved in GSCs maintenance and elucidate the mechanisms underlying their regulation.MethodsWe analyzed RNA-seq data and H3K27ac ChIP-seq data from GSE119776 to identify differentially expressed genes and enhancers, respectively. Gene Ontology analysis was performed for functional enrichment. Transcription factors were predicted using the Toolkit for Cistrome Data Browser. Prognostic analysis and gene expression correlation was conducted using the Chinese Glioma Genome Atlas (CGGA) data. Two GSC cell lines, GSC-A172 and GSC-U138MG, were isolated from A172 and U138MG cell lines. qRT-PCR was used to detect gene transcription levels. ChIP-qPCR was used to detect H3K27ac of enhancers, and binding of E2F4 to target gene enhancers. Western blot was used to analyze protein levels of p-ATR and γH2AX. Sphere formation, limiting dilution and cell growth assays were used to analyze GSCs growth and self-renewal.ResultsWe found that upregulated genes in GSCs were associated with ataxia-telangiectasia-mutated-and-Rad3-related kinase (ATR) pathway activation, and that seven enhancer-controlled genes related to ATR pathway activation (LIN9, MCM8, CEP72, POLA1, DBF4, NDE1, and CDKN2C) were identified. Expression of these genes corresponded to poor prognosis in glioma patients. E2F4 was identified as a transcription factor that regulates enhancer-controlled genes related to the ATR pathway activation, with MCM8 having the highest hazard ratio among genes positively correlated with E2F4 expression. E2F4 bound to MCM8 enhancers to promote its transcription. Overexpression of MCM8 partially restored the inhibition of GSCs self-renewal, cell growth, and the ATR pathway activation caused by E2F4 knockdown.ConclusionOur study demonstrated that E2F4-mediated enhancer activation of MCM8 promotes the ATR pathway activation and GSCs characteristics. These findings offer promising targets for the development of new therapies for gliomas.
| S-EPMC10286446 | biostudies-literature
Project description:Pertussis toxin (PTX) is a required co-adjuvant for experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin antigen. However, PTX's effects on EAE induced by the transfer of myelin-specific T helper cells is not known. Therefore, we investigated how PTX affects the Th17 transfer EAE model (Th17-EAE). We found that PTX significantly reduced Th17-EAE by inhibiting chemokine-receptor-dependent trafficking of Th17 cells. Strikingly, PTX also promoted the accumulation of B cells in the CNS, suggesting that PTX alters the disease toward a B-cell-dependent pathology. To determine the role of B cells, we compared the effects of PTX on Th17-EAE in wild-type (WT) and B-cell-deficient (µMT) mice. Without PTX treatment, disease severity was equivalent between WT and µMT mice. In contrast, with PTX treatment, the µMT mice had significantly less disease and a reduction in pathogenic Th17 cells in the CNS compared to the WT mice. In conclusion, this study shows that PTX inhibits the migration of pathogenic Th17 cells, while promoting the accumulation of pathogenic B cells in the CNS during Th17-EAE. These data provide useful methodological information for adoptive-transfer Th17-EAE and, furthermore, describe another important experimental system to study the pathogenic mechanisms of B cells in multiple sclerosis.
| S-EPMC7998427 | biostudies-literature
Project description:BackgroundT cell activation leads to increased expression of the receptor for the iron transporter transferrin (TfR) to provide iron required for the cell differentiation and clonal expansion that takes place during the days after encounter with a cognate antigen. However, T cells mobilise TfR to their surface within minutes after activation, although the reason and mechanism driving this process remain unclear.ResultsHere we show that T cells transiently increase endocytic uptake and recycling of TfR upon activation, thereby boosting their capacity to import iron. We demonstrate that increased TfR recycling is powered by a fast endocytic sorting pathway relying on the membrane proteins flotillins, Rab5- and Rab11a-positive endosomes. Our data further reveal that iron import is required for a non-canonical signalling pathway involving the kinases Zap70 and PAK, which controls adhesion of the integrin LFA-1 and eventually leads to conjugation with antigen-presenting cells.ConclusionsAltogether, our data suggest that T cells boost their iron importing capacity immediately upon activation to promote adhesion to antigen-presenting cells.
| S-EPMC9400314 | biostudies-literature
Project description:Staphylococcus aureus is an aggressive pathogen and a model organism to study cell division in sequential orthogonal planes in spherical bacteria. However, the small size of staphylococcal cells has impaired analysis of changes in morphology during the cell cycle. Here we use super-resolution microscopy and determine that S. aureus cells are not spherical throughout the cell cycle, but elongate during specific time windows, through peptidoglycan synthesis and remodelling. Both peptidoglycan hydrolysis and turgor pressure are required during division for reshaping the flat division septum into a curved surface. In this process, the septum generates less than one hemisphere of each daughter cell, a trait we show is common to other cocci. Therefore, cell surface scars of previous divisions do not divide the cells in quadrants, generating asymmetry in the daughter cells. Our results introduce a need to reassess the models for division plane selection in cocci.
| S-EPMC4557339 | biostudies-literature