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Mechanical coherence of cell layers is essential for epithelia to function as tissue barriers and to control active tissue dynamics during morphogenesis. RhoA signaling at adherens junctions plays a key role in this process by coupling cadherin-based cell-cell adhesion together with actomyosin contractility. Here we propose and analyze a mathematical model representing core interactions involved in the spatial localization of junctional RhoA signaling. We demonstrate how the interplay between biochemical signaling through positive feedback, combined with diffusion on the cell membrane and mechanical forces generated in the cortex, can determine the spatial distribution of RhoA signaling at cell-cell junctions. This dynamical mechanism relies on the balance between a propagating bistable signal that is opposed by an advective flow generated by an actomyosin stress gradient. Experimental observations on the behavior of the system when contractility is inhibited are in qualitative agreement with the predictions of the model.
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http://dx.doi.org/10.1371/journal.pcbi.1005411 | DOI Listing |
EMBO J
September 2025
Department of Biology, University of Crete, Vassilika Vouton, Heraklion, 70013, Greece.
In the presence of chromatin bridges in cytokinesis, human cells retain actin-rich structures (actin patches) at the base of the intercellular canal to prevent chromosome breakage. Here, we show that daughter nuclei connected by chromatin bridges are under mechanical tension that requires interaction of the nuclear membrane Sun1/2-Nesprin-2 Linker of Nucleoskeleton and Cytoskeleton (LINC) complex with the actin cytoskeleton, and an intact nuclear lamina. This nuclear tension promotes accumulation of Sun1/2-Nesprin-2 proteins at the base of chromatin bridges and local enrichment of the RhoA-activator PDZ RhoGEF through PDZ-binding to cytoplasmic Nesprin-2 spectrin repeats.
View Article and Find Full Text PDFJ Thromb Haemost
September 2025
Key Laboratory of Thrombosis and Hemostasis of National Health Commission, Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China; Engineering Center of Hematological Disease of Ministry of Education, Cyrus Tang Hematology Center, Collaborative Innovation
Background: Megakaryocyte (MK) fragmentation into proplatelets (PPTs) and microparticles (MKMPs) is well established, yet the mechanisms underlying MKMP generation remain unclear.
Objectives: In order to investigate the role of integrin β3 and cytoskeletal dynamics during megakaryopoiesis and explore potential therapeutic targets for thrombocytopenia.
Methods: Proplatelet formation and MKMP release were evaluated both in vivo and in vitro under integrin β3 receptor impaired environment.
Sci Adv
September 2025
School of Engineering and Materials Science, Queen Mary University of London, UK.
During heart disease, the cardiac extracellular matrix (ECM) undergoes a structural and mechanical transformation. Cardiomyocytes sense the mechanical properties of their environment, leading to phenotypic remodeling. A critical component of the ECM mechanosensing machinery, including the protein talin, is organized at the cardiomyocyte costamere.
View Article and Find Full Text PDFFASEB Bioadv
August 2025
Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Beijing Stomatological Hospital, School of Stomatology, Capital Medical University Beijing China.
Previous studies reported the pro-osteogenic ability of L-Tryptophan (L-Trp) and Calcium-Sensing RCeceptor (CaSR) respectively. Recent researchers found L-Trp could activate CaSR. Therefore, this study investigated the osteogenic mechanisms of L-Trp through CaSR activation.
View Article and Find Full Text PDFFree Radic Biol Med
September 2025
Thrombosis Research Center, Universidad de Talca, Talca, 3460000, Chile; Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Universidad de Talca, Talca, 3460000, Chile. Electronic address:
Arachidonic acid metabolism through cyclooxygenase (COX) and lipoxygenase (LOX) pathways is fundamental to inflammation, vascular homeostasis, and neuronal signaling. Here, we investigated the roles of platelet-expressed COX (PTGS1) and LOX (ALOX12) isoforms in amyloid-β (Aβ) secretion, a process implicated in the pathogenesis of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD). Using an integrative approach combining bioinformatic protein-protein interaction mapping, pathway enrichment analysis, and experimental validation, we identified extensive networks linking PTGS and ALOX isoforms to cytoskeletal remodeling, mitochondrial function, and vesicle trafficking.
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