Planar supported lipid bilayers (PSLB) presenting T cell receptor (TCR) ligands and ICAM-1 induce budding of extracellular microvesicles enriched in functional TCR, defined here as synaptic ectosomes (SE), from helper T cells. SE bind peptide-MHC directly exporting TCR into the synaptic cleft, but incorporation of other effectors is unknown. Here, we utilized bead supported lipid bilayers (BSLB) to capture SE from single immunological synapses (IS), determined SE composition by immunofluorescence flow cytometry and enriched SE for proteomic analysis by particle sorting. We demonstrate selective enrichment of CD40L and ICOS in SE in response to addition of CD40 and ICOSL, respectively, to SLB presenting TCR ligands and ICAM-1. SE are enriched in tetraspanins, BST-2, TCR signaling and ESCRT proteins. Super-resolution microscopy demonstrated that CD40L is present in microclusters within CD81 defined SE that are spatially segregated from TCR/ICOS/BST-2. CD40L SE retain the capacity to induce dendritic cell maturation and cytokine production.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748831 | PMC |
| http://dx.doi.org/10.7554/eLife.47528 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Recombinant human plasma gelsolin suppresses persistent neuroinflammation and restores hippocampal neurogenesis in murine model of decompression sickness.
J Neurophysiol
December 2024
Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, Maryland, United States.
Article Synopsis
- - The study investigates the role of plasma gelsolin (pGSN), a protein that breaks down actin filaments, in inflammatory and neurodegenerative diseases, particularly in a mouse model of decompression sickness (DCS).
- - Mice exposed to high pressure showed a significant decrease in pGSN levels and increased inflammatory microparticles (MPs), which led to neuroinflammation and cognitive/motor function impairments lasting over 12 days.
- - Administering recombinant human plasma gelsolin (rhu-pGSN) effectively reduced inflammation, restored synaptic protein levels, and improved neurological function, suggesting that rhu-pGSN could be a potential treatment for DCS.
The Six-Transmembrane Enzyme GDE2 Is Required for the Release of Molecularly Distinct Small Extracellular Vesicles from Neurons.
Cells
August 2024
The Solomon Snyder Department of Neuroscience, The Johns Hopkins School of Medicine, 725 N Wolfe Street, Baltimore, MD 21205, USA.
Extracellular vesicles (EVs) are implicated in a multitude of physiological and pathophysiological processes in the nervous system; however, their biogenesis and cargoes are not well defined. Glycerophosphodiester Phosphodiesterase 2 (GDE2 or GDPD5) is a six-transmembrane protein that cleaves the Glycosylphosphatidylinositol (GPI)-anchor that tethers some proteins to the membrane and has important roles in neurodevelopment and disease-relevant pathways of neuronal survival. We show here that GDE2 regulates the number of small EVs (sEVs) released from the cell surface of neurons via its GPI-anchor cleavage activity and contributes to the loading of protein cargo through enzymatic and non-enzymatic mechanisms.
View Article and Find Full Text PDFT Cell Immunological Synaptosomes: Definition and Isolation.
Methods Mol Biol
May 2023
School of Life Sciences, Immune Synapse and Cell Therapy Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea.
In addition to microvilli's role as structural scaffold for TCR clustering, we recently discovered a novel function as message senders. We found that microvilli are separated from the T cell body shortly upon TCR stimulation and vesiculated to form T cell microvilli particles (TMPs), a new type of membrane vesicles. TMPs and synaptic ectosomes, which bud from the synaptic cleft, constitute "T cell immunological synaptosomes (TISs)" and act as conveyors of T cell messages or traits to cognate antigen-presenting cells.
View Article and Find Full Text PDFThe Cell Biology of Tau Secretion.
Front Mol Neurosci
September 2020
Neuroscience Center, HiLIFE, University of Helsinki, Helsinki, Finland.
The progressive accumulation and spread of misfolded tau protein in the nervous system is the hallmark of tauopathies, progressive neurodegenerative diseases with only symptomatic treatments available. A growing body of evidence suggests that spreading of tau pathology can occur cell-to-cell transfer involving secretion and internalization of pathological forms of tau protein followed by templated misfolding of normal tau in recipient cells. Several studies have addressed the cell biological mechanisms of tau secretion.
View Article and Find Full Text PDFVesicular Transport of Encapsulated microRNA between Glial and Neuronal Cells.
Int J Mol Sci
July 2020
Alchem Biotech Research, Toronto, ON M5S1A8, Canada.
Exosomes (EXs) and extracellular microvesicles (EMVs) represent a diverse assortment of plasma membrane-derived nanovesicles, 30-1000 nm in diameter, released by all cell lineages of the central nervous system (CNS). They are examples of a very active and dynamic form of extracellular communication and the conveyance of biological information transfer essential to maintain homeostatic neurological functions and contain complex molecular cargoes representative of the cytoplasm of their cells of origin. These molecular cargoes include various mixtures of proteins, lipids, proteolipids, cytokines, chemokines, carbohydrates, microRNAs (miRNA) and messenger RNAs (mRNA) and other components, including end-stage neurotoxic and pathogenic metabolic products, such as amyloid beta (Aβ) peptides.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!