The BCR relays extracellular signals and internalizes Ag for processing and presentation. We have previously demonstrated that ligation of the BCR destabilizes Ig-alpha/Ig-beta (Ig-alphabeta) from mu-H chain (mum). In this study we report that receptor destabilization represents a physical separation of mum from Ig-alphabeta. Sucrose gradient fractionation localized Ig-alphabeta to G(M1)-containing lipid microdomains in the absence of mum. Confocal and electron microscopy studies revealed the colocalization of unsheathed mum with clathrin-coated vesicles. Furthermore, mum failed to associate with clathrin-coated vesicles when receptor destabilization was inhibited, suggesting that unsheathing of mum is required for clathrin-mediated endocytosis. In summary, we found that Ag stimulation physically separates Ig-alphabeta from mum, facilitating concomitant signal transduction and Ag delivery to the endocytic compartment.
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http://dx.doi.org/10.4049/jimmunol.175.1.147 | DOI Listing |
J Biomol Struct Dyn
January 2025
Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Cancer sparks if the components of the cellular signaling network are aberrantly activated, leading to uncontrolled cell growth and proliferation. One of the most important players of this highly regulated network is the Wnt/β-catenin signaling, with a significant role in human health and disease. The critical co-receptor of this pathway, LRP6, is overexpressed in various cancer types and is a target for therapy.
View Article and Find Full Text PDFCell Death Dis
January 2025
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Macrophages play important roles in maintaining intestinal homeostasis and in the pathogenesis of inflammatory bowel diseases (IBDs). However, the underlying mechanisms that govern macrophage-mediated inflammation are still largely unknown. In this study, we report that RNF128 is downregulated in proinflammatory macrophages.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Paramyxoviruses are significant human and animal pathogens that include mumps virus (MuV), Newcastle disease virus (NDV) and the murine parainfluenza virus Sendai (SeV). Despite their importance, few host factors implicated in paramyxovirus infection are known. Using a recombinant SeV expressing destabilized eGFP (rSeVCdseGFP) in a loss-of-function CRISPR screen, we identified the CMP-sialic acid transporter (CST) gene SLC35A1 and the UDP-galactose transporter (UGT) gene SLC35A2 as essential for paramyxovirus infection.
View Article and Find Full Text PDFPhytomedicine
October 2024
Department of Rheumatology and Immunology, The First Hospital of China Medical University, Shenyang 110001, PR China. Electronic address:
Background: In the context of osteoarthritis (OA), a condition marked by joint degeneration, there is a notable absence of efficacious approaches to promote regenerative healing in chondrocytes. Novel therapeutic strategies like nanomicelles-hydrogel microspheres loaded with Astragalus polysaccharide (GelMA@APPA) offer promising avenues for promoting chondrocyte regeneration and mitigating OA progression.
Methods: Astragalus polysaccharide (APS) has been shown to induce chondrocyte proliferation and promote cartilage matrix secretion, demonstrating biological activity associated with chondrocyte regeneration.
Nat Commun
January 2025
Institute of Developmental Biology and Neurobiology, Faculty of Biology, Johannes Gutenberg University Mainz, Mainz, Germany.
After a peripheral nerve injury, Schwann cells (SCs), the myelinating glia of the peripheral nervous system, convert into repair cells that foster axonal regrowth, and then remyelinate or re-ensheath regenerated axons, thereby ensuring functional recovery. The efficiency of this mechanism depends however on the time needed for axons to regrow. Here, we show that ablation of histone deacetylase 8 (HDAC8) in SCs accelerates the regrowth of sensory axons and sensory function recovery.
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