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ATP and noradrenaline activate CREB in astrocytes via noncanonical Ca 2+ and cyclic AMP independent pathways
Author(s) -
Carriba Paulina,
Pardo Luis,
ParraDamas Arnaldo,
Lichtenstein Mathieu P.,
Saura Carlos A.,
Pujol Aurora,
Masgrau Roser,
Galea Elena
Publication year - 2012
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22352
Subject(s) - creb , biology , cyclic amp response element binding protein , microbiology and biotechnology , transcription factor , activating transcription factor , protein kinase a , protein kinase c , activator (genetics) , response element , transcription (linguistics) , creb1 , synaptic plasticity , signal transduction , phosphorylation , promoter , biochemistry , gene expression , receptor , gene , linguistics , philosophy
In neurons, it is well established that CREB contributes to learning and memory by orchestrating the translation of experience into the activity‐dependent (i.e., driven by neurotransmitters) transcription of plasticity‐related genes. The activity‐dependent CREB‐triggered transcription requires the concerted action of cyclic AMP/protein kinase A and Ca 2+ /calcineurin via the CREB‐regulated transcription co‐activator (CRTC). It is not known, however, whether a comparable molecular sequence occurs in astrocytes, despite the unquestionable contribution of these cells to brain plasticity. Here we sought to determine whether and how ATP and noradrenaline cause CREB‐dependent transcription in rat cortical astrocyte cultures. Both transmitters induced CREB phosphorylation (Western Blots), CREB‐dependent transcription (CRE‐luciferase reporter assays), and the transcription of Bdnf, a canonical regulator of synaptic plasticity (quantitative RT‐PCR). We indentified a Ca 2+ and diacylglycerol‐independent protein kinase C at the uppermost position of the cascade leading to CREB‐dependent transcription. Notably, CREB‐dependent transcription was partially dependent on ERK1/2 and CRTC, but independent of cyclic AMP/protein kinase A or Ca 2+ /calcineurin. We conclude that ATP and noradrenaline activate CREB‐dependent transcription in cortical astrocytes via an atypical protein kinase C. It is of relevance that the signaling involved be starkly different to the one described in neurons since there is no convergence of Ca 2+ and cyclic AMP‐dependent pathways on CRTC, which, moreover, exerts a modulatory rather than a central role. Our data thus point to the existence of an alternative, non‐neuronal, glia‐based role of CREB in plasticity. © 2012 Wiley Periodicals, Inc.