title: REST/NRSF governs the expression of dense-core vesicle gliosecretion in astrocytes.
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.
authors.affiliation: San Raffaele Scientific Institute, 20132 Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Prada
authors.forename: Julie
authors.initials: J
authors.lastname: Marchaland
authors.forename: Paola
authors.initials: P
authors.lastname: Podini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Magrassi
authors.forename: Rosalba
authors.initials: R
authors.lastname: D'Alessandro
authors.forename: Paola
authors.initials: P
authors.lastname: Bezzi
authors.forename: Jacopo
authors.initials: J
authors.lastname: Meldolesi
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D005089:Exocytosis; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D053381:Secretogranin II / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D049452:Green Fluorescent Proteins; D009478:Neuropeptide Y; D012097:Repressor Proteins; D053381:Secretogranin II; D000099229:RE1-Silencing Transcription Factor; C506135:SCG2 protein, human; C506141:secretogranin 2, rat