RGD Reference Report - REST/NRSF governs the expression of dense-core vesicle gliosecretion in astrocytes. - Rat Genome Database

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

Authors: Prada, I  Marchaland, J  Podini, P  Magrassi, L  D'Alessandro, R  Bezzi, P  Meldolesi, J 
Citation: Prada I, etal., J Cell Biol. 2011 May 2;193(3):537-49. doi: 10.1083/jcb.201010126.
RGD ID: 8554180
Pubmed: PMID:21536750   (View Abstract at PubMed)
PMCID: PMC3087003   (View Article at PubMed Central)
DOI: DOI:10.1083/jcb.201010126   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of calcium ion-dependent exocytosis involved_inIMP 8554180PMID:21536750UniProt 
negative regulation of dense core granule biogenesis involved_inIMP 8554180PMID:21536750UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
nucleus located_inIDA 8554180PMID:21536750UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Rest  (RE1-silencing transcription factor)

Additional Information