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Astrocytic extracellular vesicles modulate neuronal calcium homeostasis via transglutaminase-2
by
Boocock, David J
, Mazzanti, Michele
, Elisabetta Am Verderio
, Coveney, Clare
, Tonoli, Elisa
, Savoca, Maria Pia
, Prada, Ilaria
, Verderio, Claudia
, Verduci, Ivan
, caia, Greta
, Gabrielli, Martina
, Sancini, Giulio
in
Astrocytes
/ Brain slice preparation
/ Calcium (extracellular)
/ Calcium (intracellular)
/ Calcium channels (L-type)
/ Calcium homeostasis
/ Calcium imaging
/ Calcium influx
/ Extracellular vesicles
/ Hippocampus
/ Homeostasis
/ Na+/Ca2+ exchanger
/ Na+/K+-exchanging ATPase
/ Neuroimaging
/ Neuroscience
/ Proteomics
/ Transglutaminase 2
2021
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Astrocytic extracellular vesicles modulate neuronal calcium homeostasis via transglutaminase-2
by
Boocock, David J
, Mazzanti, Michele
, Elisabetta Am Verderio
, Coveney, Clare
, Tonoli, Elisa
, Savoca, Maria Pia
, Prada, Ilaria
, Verderio, Claudia
, Verduci, Ivan
, caia, Greta
, Gabrielli, Martina
, Sancini, Giulio
in
Astrocytes
/ Brain slice preparation
/ Calcium (extracellular)
/ Calcium (intracellular)
/ Calcium channels (L-type)
/ Calcium homeostasis
/ Calcium imaging
/ Calcium influx
/ Extracellular vesicles
/ Hippocampus
/ Homeostasis
/ Na+/Ca2+ exchanger
/ Na+/K+-exchanging ATPase
/ Neuroimaging
/ Neuroscience
/ Proteomics
/ Transglutaminase 2
2021
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Astrocytic extracellular vesicles modulate neuronal calcium homeostasis via transglutaminase-2
by
Boocock, David J
, Mazzanti, Michele
, Elisabetta Am Verderio
, Coveney, Clare
, Tonoli, Elisa
, Savoca, Maria Pia
, Prada, Ilaria
, Verderio, Claudia
, Verduci, Ivan
, caia, Greta
, Gabrielli, Martina
, Sancini, Giulio
in
Astrocytes
/ Brain slice preparation
/ Calcium (extracellular)
/ Calcium (intracellular)
/ Calcium channels (L-type)
/ Calcium homeostasis
/ Calcium imaging
/ Calcium influx
/ Extracellular vesicles
/ Hippocampus
/ Homeostasis
/ Na+/Ca2+ exchanger
/ Na+/K+-exchanging ATPase
/ Neuroimaging
/ Neuroscience
/ Proteomics
/ Transglutaminase 2
2021
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Astrocytic extracellular vesicles modulate neuronal calcium homeostasis via transglutaminase-2
Paper
Astrocytic extracellular vesicles modulate neuronal calcium homeostasis via transglutaminase-2
2021
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Overview
We have uncovered a novel role for astrocytes-derived extracellular vesicles (EVs) in controlling intraneuronal Ca2+ concentration ([Ca2+]i) and identified transglutaminase-2 (TG2) as a surface-cargo of astrocytes-derived EVs. Incubation of hippocampal neurons with primed astrocyte-derived EVs have led to an increase in [Ca2+]i, unlike EVs from TG2-knockout astrocytes. Exposure of neurons or brain slices to extracellular TG2 promoted a [Ca2+]i rise, which was reversible upon TG2 removal and was dependent on Ca2+ influx through the plasma membrane. Patch-clamp and calcium imaging recordings revealed TG2-dependent neuronal membrane depolarisation and activation of inward currents, due to the opening of L-type-VOCCs and to Na+/Ca2+-exchanger (NCX) operation in the reverse mode, as indicated by VOCCs/NCX pharmacological inhibitors. A subunit of Na+/K+-ATPase was selected by comparative proteomics and identified as being functionally inhibited by extracellular TG2, implicating Na+/K+-ATPase inhibition in NCX reverse mode-switching leading to Ca2+ influx and higher basal [Ca2+]i. These data suggest that reactive astrocytes control intraneuronal [Ca2+]i through release of EVs with TG2 as responsible cargo, which could have a significant impact on synaptic activity in brain inflammation. Competing Interest Statement The authors have declared no competing interest. Footnotes * Extended View figures/tables (Fig. EV1, EV2, EV3; Table EV1) and Appendix (extended methods and Supplementary Table S1) have been added
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
Subject
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