CREB decreases astrocytic excitability by modifying subcellular calcium fluxes via the sigma-1 receptor
Eraso-Pichot, Abel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Larramona Arcas, Raquel (Universitat Autònoma de Barcelona. Institut de Neurociències)
Vicario-Orri, E. (Universitat Autònoma de Barcelona. Institut de Neurociències)
Villalonga, R. (Universitat Autònoma de Barcelona. Institut de Neurociències)
Pardo Fernández, Luis (Universitat Autònoma de Barcelona. Institut de Neurociències)
Galea, Elena (Universitat Autònoma de Barcelona. Institut de Neurociències)
Masgrau Juanola, Roser (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2016
Abstract:	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.
Grants:	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
Note:	Altres ajuts: La Marató de TV3 (TV3-20141430)
Rights:	Tots els drets reservats.
Language:	Anglès
Document:	Article ; recerca ; Versió acceptada per publicar
Subject:	Calcium signalling ; Endoplasmic reticulum ; Mitochondria ; Mitochondria-associated membranes ; MCU ; VP16-CREB ; CEPIA indicators
Published in:	Cellular and Molecular Life Sciences, Vol. 74, no. 5 (March 2017) , p. 937-950, ISSN 1420-9071

DOI: 10.1007/s00018-016-2397-5
PMID: 27761593

Post-print 26 p, 3.6 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles