visitante ::
identificación
|
|||||||||||||||
Buscar | Enviar | Ayuda | Servicio de Bibliotecas | Sobre el DDD | Català English Español |
Página principal > Artículos > Artículos publicados > CREB decreases astrocytic excitability by modifying subcellular calcium fluxes via the sigma-1 receptor |
Fecha: | 2016 |
Resumen: | Astrocytic excitability relies on cytosolic calcium increases as a key mechanism, whereby astrocytes contribute to synaptic transmission and hence learning and memory. While it is a cornerstone of neurosciences that experiences are remembered, because transmitters activate gene expression in neurons, long-term adaptive astrocyte plasticity has not been described. Here, we investigated whether the transcription factor CREB mediates adaptive plasticity-like phenomena in astrocytes. We found that activation of CREB-dependent transcription reduced the calcium responses induced by ATP, noradrenaline, or endothelin-1. As to the mechanism, expression of VP16-CREB, a constitutively active CREB mutant, had no effect on basal cytosolic calcium levels, extracellular calcium entry, or calcium mobilization from lysosomal-related acidic stores. Rather, VP16-CREB upregulated sigma-1 receptor expression thereby increasing the release of calcium from the endoplasmic reticulum and its uptake by mitochondria. Sigma-1 receptor was also upregulated in vivo upon VP16-CREB expression in astrocytes. We conclude that CREB decreases astrocyte responsiveness by increasing calcium signalling at the endoplasmic reticulum-mitochondria interface, which might be an astrocyte-based form of long-term depression. |
Ayudas: | Ministerio de Economía y Competitividad BFU2010-21921 Ministerio de Economía y Competitividad BFU2012-38844 Agència de Gestió d'Ajuts Universitaris i de Recerca 2005/SGR-00719 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-00984 Ministerio de Educación, Cultura y Deporte FPU-13/05377 |
Nota: | Altres ajuts: La Marató de TV3 (TV3-20141430) |
Derechos: | Tots els drets reservats. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió acceptada per publicar |
Materia: | Calcium signalling ; Endoplasmic reticulum ; Mitochondria ; Mitochondria-associated membranes ; MCU ; VP16-CREB ; CEPIA indicators |
Publicado en: | Cellular and Molecular Life Sciences, Vol. 74, no. 5 (March 2017) , p. 937-950, ISSN 1420-9071 |
Post-print 26 p, 3.6 MB |