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REST/NRSF governs the expression of dense-core vesicle gliosecretion in astrocytes
- Source :
- Journal of Cell Biology, vol. 193, no. 3, pp. 537-549, The Journal of Cell Biology
- Publication Year :
- 2011
-
Abstract
- The REST/NRSF transcriptional repressor prevents cultured astrocytes from forming DCVs, and its variable expression in human brain cortex astrocytes may account for their functional heterogeneity.<br />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 Ca2+-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.
- Subjects :
- medicine.medical_specialty
Cellular differentiation
Green Fluorescent Proteins
Biology
PC12 Cells
Corrections
Exocytosis
Article
Internal medicine
medicine
Animals
Humans
Neuropeptide Y
Transcription factor
Research Articles
Astrocytes/metabolism
Brain/metabolism
Green Fluorescent Proteins/metabolism
Kinetics
Neuroglia/metabolism
Neurons/metabolism
Neuropeptide Y/metabolism
Rats
Repressor Proteins/metabolism
Secretogranin II/metabolism
Secretory Vesicles/metabolism
Neurons
Microglia
Secretory Vesicles
REST
astrocytes
Brain
Correction
Transfection
Cell Biology
secretion
Neuropeptide Y receptor
Cell biology
Repressor Proteins
Endocrinology
medicine.anatomical_structure
Membrane protein
Secretogranin II
Neuroglia
Astrocyte
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Journal of Cell Biology, vol. 193, no. 3, pp. 537-549, The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....9b611e867bf890771435f7fddb17b0c5