CREB decreases astrocytic excitability by modifying subcellular calcium fluxes via the sigma-1 receptor
Cell. Mol. Life Sci.. 2016-10-19; 74(5): 937-950
DOI: 10.1007/s00018-016-2397-5
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1. Cell Mol Life Sci. 2017 Mar;74(5):937-950. doi: 10.1007/s00018-016-2397-5. Epub
2016 Oct 19.
CREB decreases astrocytic excitability by modifying subcellular calcium fluxes
via the sigma-1 receptor.
Eraso-Pichot A(1), Larramona-Arcas R(1), Vicario-Orri E(1)(2), Villalonga R(1),
Pardo L(1), Galea E(3)(4), Masgrau R(5).
Author information:
(1)Unitat de Bioquímica de Medicina, Departament de Bioquímica i Biologia
Molecular, Institut de Neurociències, Edifici M, Universitat Autònoma de
Barcelona, Bellaterra, 08193, Barcelona, Catalonia, Spain.
(2)Department of Neurosciences, School of Medicine, University of California,
9500 Gilman Dr, La Jolla, CA, 92093, USA.
(3)Unitat de Bioquímica de Medicina, Departament de Bioquímica i Biologia
Molecular, Institut de Neurociències, Edifici M, Universitat Autònoma de
Barcelona, Bellaterra, 08193, Barcelona, Catalonia, Spain. .
(4)Institució Catalana De Recerca I Estudis Avançats (ICREA), Passeig Lluís
Companys 23, 08010, Barcelona, Catalonia, Spain. .
(5)Unitat de Bioquímica de Medicina, Departament de Bioquímica i Biologia
Molecular, Institut de Neurociències, Edifici M, Universitat Autònoma de
Barcelona, Bellaterra, 08193, Barcelona, Catalonia, Spain. .
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.
DOI: 10.1007/s00018-016-2397-5
PMID: 27761593 [Indexed for MEDLINE]