Exocytosis of large-diameter lysosomes mediates interferon γ-induced relocation of MHC class II molecules toward the surface of astrocytes
| العنوان: | Exocytosis of large-diameter lysosomes mediates interferon γ-induced relocation of MHC class II molecules toward the surface of astrocytes |
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| المؤلفون: | Alexei Verkhratsky, Mićo Božić, Robert Zorec, Matjaž Stenovec |
| المصدر: | Božić, M, Verkhratsky, A, Zorec, R & Stenovec, M 2019, ' Exocytosis of large-diameter lysosomes mediates interferon γ-induced relocation of MHC class II molecules toward the surface of astrocytes ', Cellular and Molecular Life Sciences . https://doi.org/10.1007/s00018-019-03350-8Test Cellular and Molecular Life Sciences Cellular and molecular life sciences, vol. 77, no. 16, pp. 3245-3264, 2020. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Central Nervous System, Immunolabeling, Astroglia, 0302 clinical medicine, Cells, Cultured, fuzijske pore, Antigen Presentation, Chemistry, respiratory system, Inflammatory cytokines, Endocytosis, Astrogliosis, Cell biology, Protein Transport, medicine.anatomical_structure, Molecular Medicine, Original Article, Female, Patch clamp, obliž, Astrocyte, Endosome, Antigen presentation, Adaptive immunity, chemical and pharmacologic phenomena, vnetni citokini, Endosomes, Exocytosis, 03 medical and health sciences, Cellular and Molecular Neuroscience, Interferon-gamma, medicine, Animals, Rats, Wistar, Molecular Biology, Neuroinflammation, Pharmacology, Inflammation, adaptivna imunost, Secretory Vesicles, Cell Membrane, Histocompatibility Antigens Class II, Cell Biology, medicine.disease, lizosomi, Fusion pore, Rats, 030104 developmental biology, Astrocytes, udc:616-092, Lysosomes, 030217 neurology & neurosurgery, Biomarkers |
| الوصف: | Astrocytes are the key homeostatic cells in the central nervous system; initiation of reactive astrogliosis contributes to neuroinflammation. Pro-inflammatory cytokine interferon γ (IFNγ) induces the expression of the major histocompatibility complex class II (MHCII) molecules, involved in antigen presentation in reactive astrocytes. The pathway for MHCII delivery to the astrocyte plasma membrane, where MHCII present antigens, is unknown. Rat astrocytes in culture and in organotypic slices were exposed to IFNγ to induce reactive astrogliosis. Astrocytes were probed with optophysiologic tools to investigate subcellular localization of immunolabeled MHCII, and with electrophysiology to characterize interactions of single vesicles with the plasmalemma. In culture and in organotypic slices, IFNγ augmented the astrocytic expression of MHCII, which prominently co-localized with lysosomal marker LAMP1-EGFP, modestly co-localized with Rab7, and did not co-localize with endosomal markers Rab4A, EEA1, and TPC1. MHCII lysosomal localization was corroborated by treatment with the lysosomolytic agent glycyl-l-phenylalanine-β-naphthylamide, which reduced the number of MHCII-positive vesicles. The surface presence of MHCII was revealed by immunolabeling of live non-permeabilized cells. In IFNγ-treated astrocytes, an increased fraction of large-diameter exocytotic vesicles (lysosome-like vesicles) with prolonged fusion pore dwell time and larger pore conductance was recorded, whereas the rate of endocytosis was decreased. Stimulation with ATP, which triggers cytosolic calcium signaling, increased the frequency of exocytotic events, whereas the frequency of full endocytosis was further reduced. In IFNγ-treated astrocytes, MHCII-linked antigen surface presentation is mediated by increased lysosomal exocytosis, whereas surface retention of antigens is prolonged by concomitant inhibition of endocytosis. Electronic supplementary material The online version of this article (10.1007/s00018-019-03350-8) contains supplementary material, which is available to authorized users. |
| وصف الملف: | application/pdf; text/url |
| اللغة: | English |
| تدمد: | 1420-682X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ddb3551110bfc383435c30d530f8753dTest https://www.research.manchester.ac.uk/portal/en/publications/exocytosis-of-largediameter-lysosomes-mediates-interferon-induced-relocation-of-mhc-class-ii-molecules-toward-the-surface-of-astrocytesTest(2e147911-aa1d-44d3-b274-fda67d7e8b47).html |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ddb3551110bfc383435c30d530f8753d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1420682X |
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