Extracellular microvesicles from astrocytes contain functional glutamate transporters: regulation by protein kinase C and cell activation.

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_F08A8A9B5143
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Extracellular microvesicles from astrocytes contain functional glutamate transporters: regulation by protein kinase C and cell activation.
Périodique
Frontiers in Cellular Neuroscience
Auteur(s)
Gosselin R.D., Meylan P., Decosterd I.
ISSN
1662-5102 (Electronic)
ISSN-L
1662-5102
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
7
Numéro
251
Pages
1-15
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: epublish
Résumé
Glutamate transport through astrocytic excitatory amino-acid transporters (EAAT)-1 and EAAT-2 is paramount for neural homeostasis. EAAT-1 has been reported in secreted extracellular microvesicles (eMV, such as exosomes) and because the protein kinase C (PKC) family controls the sub-cellular distribution of EAATs, we have explored whether PKCs drive EAATs into eMV. Using rat primary astrocytes, confocal immunofluorescence and ultracentrifugation on sucrose gradient we here report that PKC activation by phorbol myristate acetate (PMA) reorganizes EAAT-1 distribution and reduces functional [(3)H]-aspartate reuptake. Western-blots show that EAAT-1 is present in eMV from astrocyte conditioned medium, together with NaK ATPase and glutamine synthetase all being further increased after PMA treatment. However, nanoparticle tracking analysis reveals that PKC activation did not change particle concentration. Functional analysis indicates that eMV have the capacity to reuptake [(3)H]-aspartate. In vivo, we demonstrate that spinal astrocytic reaction induced by peripheral nerve lesion (spared nerve injury, SNI) is associated with a phosphorylation of PKC δ together with a shift of EAAT distribution ipsilaterally. Ex vivo, spinal explants from SNI rats release eMV with an increased content of NaK ATPase, EAAT-1 and EAAT-2. These data indicate PKC and cell activation as important regulators of EAAT-1 incorporation in eMV, and raise the possibility that microvesicular EAAT-1 may exert extracellular functions. Beyond a putative role in neuropathic pain, this phenomenon may be important for understanding neural homeostasis and a wide range of neurological diseases associated with astrocytic reaction as well as non-neurological diseases linked to eMV release.
Pubmed
Web of science
Open Access
Oui
Création de la notice
09/01/2014 18:52
Dernière modification de la notice
09/05/2019 3:16
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