REST/NRSF governs the expression of dense-core vesicle gliosecretion in astrocytes.

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Serval ID
serval:BIB_7A9515F0EB54
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
REST/NRSF governs the expression of dense-core vesicle gliosecretion in astrocytes.
Journal
Journal of Cell Biology
Author(s)
Prada I., Marchaland J., Podini P., Magrassi L., D'Alessandro R., Bezzi P., Meldolesi J.
ISSN
1540-8140 (Electronic)
ISSN-L
0021-9525
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
193
Number
3
Pages
537-549
Language
english
Abstract
Astrocytes are the brain nonnerve cells that are competent for gliosecretion, i.e., for expression and regulated exocytosis of clear and dense-core vesicles (DCVs). We investigated whether expression of astrocyte DCVs is governed by RE-1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF), the transcription repressor that orchestrates nerve cell differentiation. Rat astrocyte cultures exhibited high levels of REST and expressed neither DCVs nor their markers (granins, peptides, and membrane proteins). Transfection of a dominant-negative construct of REST induced the appearance of DCVs filled with secretogranin 2 and neuropeptide Y (NPY) and distinct from other organelles. Total internal reflection fluorescence analysis revealed NPY-monomeric red fluorescent protein-labeled DCVs to undergo Ca(2+)-dependent exocytosis, which was largely prevented by botulinum toxin B. In the I-II layers of the human temporal brain cortex, all neurons and microglia exhibited the expected inappreciable and high levels of REST, respectively. In contrast, astrocyte REST was variable, going from inappreciable to high, and accompanied by a variable expression of DCVs. In conclusion, astrocyte DCV expression and gliosecretion are governed by REST. The variable in situ REST levels may contribute to the well-known structural/functional heterogeneity of astrocytes.
Keywords
Animals, Astrocytes/metabolism, Brain/metabolism, Exocytosis, Green Fluorescent Proteins/metabolism, Humans, Kinetics, Neuroglia/metabolism, Neurons/metabolism, Neuropeptide Y/metabolism, PC12 Cells, Rats, Repressor Proteins/metabolism, Secretogranin II/metabolism, Secretory Vesicles/metabolism
Pubmed
Web of science
Create date
22/08/2011 10:48
Last modification date
20/08/2019 15:36
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