CREB decreases astrocytic excitability by modifying subcellular calcium fluxes via the sigma-1 receptor
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- 作者：A. Eraso-Pichot ; R. Larramona-Arcas…
- 关键词：Calcium signalling ; Endoplasmic reticulum ; Mitochondria ; Mitochondria ; associated membranes ; MCU ; VP16 ; CREB ; CEPIA indicators
- 刊名：Cellular and Molecular Life Sciences
- 出版年：2017
- 出版时间：March 2017
- 年：2017
- 卷：74
- 期：5
- 页码：937-950
- 全文大小：
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Cell Biology; Biomedicine, general; Life Sciences, general; Biochemistry, general;
- 出版者：Springer International Publishing
- ISSN：1420-9071
- 卷排序：74
文摘
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.