Astrocyte-secreted peptidergic and non-peptidergic transmitters regulate development, physiology and pathology of neuronal circuits (Araque et al. 2001;Volterra and Meldolesi 2005). For instance, astroglial-derived thrombospondins and ApoE-containing lipoproteins control synaptogenesis, while astrocytic glutamate, ATP and D-serine modulate synaptic transmission and network activity (Mauch et al. 2001;Fellin et al. 2004;Christopherson et al. 2005;Pascual et al. 2005;Panatier et al. 2006;Perea and Araque 2007). Moreover, proinflammatory cytokines, growth factors and amino acids released from glia have been associated with neurological disorders and neurodegenerative diseases ( Address correspondence and reprint requests to Dr Fernando Aguado, Department of Cell Biology, University of Barcelona, Av. Diagonal 645, Barcelona E-08028, Spain. E-mail: faguado@ub.eduAbbreviations used: BAPTA, 1,2-bis(2-amino-phenoxy)ethane-N, N, N¢, N¢-tetraacetic acid; GFAP, glial fibrillary acidic protein; GFP, green flourescent protein; IFN, interferon; IL, interleukin; PBS, phosphatebuffered saline; SCG-2, secretogranin-2; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SNAP, synaptosomal-associated protein; SNAREs, N-ethylmaleimide-sensitive factor attachment protein receptors; TNF, tumor necrosis factor; TPA, phorbol-12-myristate-13-acetate; VAMP, vesicle-associated membrane protein. AbstractVesicular 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.
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