Regulation of exocytotic protein expression and Ca2+-dependent peptide secretion in astrocytes.
Vesicular transmitter release from astrocytes influences neuronal development, function and plasticity. However, secretory pathways and the involved molecular mechanisms in astroglial cells are poorly known. In this study, we show that a variety of SNARE and Munc18 isoforms are expressed by cultured astrocytes, with syntaxin-4, Munc18c, SNAP-23 and VAMP-3 being the most abundant variants. Exocytotic protein expression was differentially regulated by activating and differentiating agents. Specifically, proteins controlling Ca(2+)-dependent secretion in neuroendocrine cells were up-regulated after long-term 8Br-cAMP administration in astrocytes, but not by proinflammatory cytokines. Moreover, 8Br-cAMP treatment greatly increased the cellular content of the peptidic vesicle marker secretogranin-2. Release assays performed on cAMP-treated astrocytes showed that basal and stimulated secretogranin-2 secretion are dependent on [Ca(2+)](i). As shown release of the chimeric hormone ANP.emd from transfected cells, cAMP-induced differentiation in astrocytes enhances Ca(2+)-regulated peptide secretion. We conclude that astroglial cells display distinctive molecular components for exocytosis. Moreover, the regulation of both exocytotic protein expression and Ca(2+)-dependent peptide secretion in astrocytes by differentiating and activating agents suggest that glial secretory pathways are adjusted in different physiological states.
Paco
Sonia
S
Department of Cell Biology, University of Barcelona, Barcelona, Spain.
Margelí
Maria A
MA
Olkkonen
Vesa M
VM
Imai
Akane
A
Blasi
Juan
J
Fischer-Colbrie
Reiner
R
Aguado
Fernando
F
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D002864:Chromogranins / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D051938:Munc18 Proteins / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009489:Neurosecretion / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D050600:SNARE Proteins / Q000737:chemistry / Q000378:metabolism; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D002864:Chromogranins; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D050600:SNARE Proteins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002118:Calcium