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Τύπος: Άρθρο σε επιστημονικό περιοδικό
Τίτλος: Differential intracellular trafficking of extracellular vesicles in microglia and astrocytes
Εναλλακτικός τίτλος: Ενδοκύτωση εξωσωμάτων από κύτταρα γλοίας
Συγγραφέας: [EL] Πανταζοπούλου, Μαρίνα[EN] Pantazopoulou, Marinasemantics logo
[EL] Λαμπροκωστοπούλου, Αγαρίστη[EN] Lamprokostopoulou, Agaristisemantics logo
[EL] Καράμπελα, Δήμητρα - Σωτηρία[EN] Karampela, Dimitra - Sotiriasemantics logo
[EL] Αλεξάκη, Αναστασία[EN] Alexaki, Anastasiasemantics logo
[EL] Δελής, Αναστάσιος[EN] Delis, Anastasiossemantics logo
[FR] Coens, Audreysemantics logo
[EL] Σαμιωτάκη, Μαρτίνα[EN] Samiotaki, Martinasemantics logo
[EL] Κριεμπάρδης, Αναστάσιος[EN] Kriebardis, Anastasiossemantics logo
[FR] Melki, Ronaldsemantics logo
[EL] Παγκάκης, Σταμάτης[EN] Pagakis, Stamatissemantics logo
[EL] Στεφανής, Λεωνίδας[EN] Stefanis, Leonidassemantics logo
[EL] Βεκρέλλης, Κώστας[EN] Vekrellis, Kostassemantics logo
Ημερομηνία: 30/06/2023
Περίληψη: Extracellular vesicles (EVs) have emerged as key players in cell-to-cell communication in both physiological and pathological processes in the Central Nervous System. Thus far, the intracellular pathways involved in uptake and trafficking of EVs within different cell types of the brain are poorly understood. In our study, the endocytic processes and subcellular sorting of EVs were investigated in primary glial cells, particularly linked with the EV-associated α-synuclein (α-syn) transmission. Mouse microglia and astrocytic primary cultures were incubated with DiI-stained mouse brain-derived EVs. The internalization and trafficking pathways were analyzed in cells treated with pharmacological reagents that block the major endocytic pathways. Brain-derived EVs were internalized by both glial cell types; however, uptake was more efficient in microglia than in astrocytes. Colocalization of EVs with early and late endocytic markers (Rab5, Lamp1) indicated that EVs are sorted to endo-lysosomes for subsequent processing. Blocking actin-dependent phagocytosis and/or macropinocytosis with Cytochalasin D or EIPA inhibited EV entry into glial cells, whereas treatment with inhibitors that strip cholesterol off the plasma membrane, induced uptake, however differentially altered endosomal sorting. EV-associated fibrillar α-Syn was efficiently internalized and detected in Rab5- and Lamp1-positive compartments within microglia. Our study strongly suggests that EVs enter glial cells through phagocytosis and/or macropinocytosis and are sorted to endo-lysosomes for subsequent processing. Further, brain-derived EVs serve as scavengers and mediate cell-to-glia transfer of pathological α-Syn which is also targeted to the endolysosomal pathway, suggesting a beneficial role in microglia-mediated clearance of toxic protein aggregates, present in numerous neurodegenerative diseases.
Γλώσσα: Αγγλικά
Σελίδες: 25
DOI: 10.1007/s00018-023-04841-5
EISSN: 1420-9071
Θεματική κατηγορία: [EL] Νευροεπιστήμες[EN] Neurosciencessemantics logo
Λέξεις-κλειδιά: Small extracellular vesicles (sEVs)MicrogliaAstrocytesEndocytosisEndolysosomal pathwayLysosomeAlpha-synuclein
Κάτοχος πνευματικών δικαιωμάτων: © The Author(s) 2023
Όροι και προϋποθέσεις δικαιωμάτων: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
Ηλεκτρονική διεύθυνση του τεκμηρίου στον εκδότη: https://link.springer.com/article/10.1007/s00018-023-04841-5
Ηλεκτρονική διεύθυνση περιοδικού: https://link.springer.com/journal/18
Τίτλος πηγής δημοσίευσης: Cellular and Molecular Life Sciences
Τόμος: 80
Σελίδες τεκμηρίου (στην πηγή): Article no 193
Σημειώσεις: This work was co-fnanced by Greece and the European Union (European Social Fund—ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning 2014–2020” (MIS 5049249) to MP, AL, LS, and KV.
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