TY - JOUR
T1 - REST/NRSF governs the expression of dense-core vesicle gliosecretion in astrocytes
AU - Prada, Ilaria
AU - Marchaland, Julie
AU - Podini, Paola
AU - Magrassi, Lorenzo
AU - D'Alessandro, Rosalba
AU - Bezzi, Paola
AU - Meldolesi, Jacopo
PY - 2011/5
Y1 - 2011/5
N2 - Astrocytes are the brain nonnerve cells that are competent for gliosecretion, i.e., for expression and regulated exocytosis of clear and densecore 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.
AB - Astrocytes are the brain nonnerve cells that are competent for gliosecretion, i.e., for expression and regulated exocytosis of clear and densecore 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.
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U2 - 10.1083/jcb.201010126
DO - 10.1083/jcb.201010126
M3 - Article
C2 - 21536750
AN - SCOPUS:79956206703
VL - 193
SP - 537
EP - 549
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 3
ER -