Coronin 1 regulates cognition and behavior through modulation of cAMP/protein kinase A signaling.
| Autor: | Rajesh Jayachandran, Xiaolong Liu, Somdeb Bosedasgupta, Philipp Müller, Chun-Lei Zhang, Despina Moshous, Vera Studer, Jacques Schneider, Christel Genoud, Catherine Fossoud, Frédéric Gambino, Malik Khelfaoui, Christian Müller, Deborah Bartholdi, Helene Rossez, Michael Stiess, Xander Houbaert, Rolf Jaussi, Daniel Frey, Richard A Kammerer, Xavier Deupi, Jean-Pierre de Villartay, Andreas Lüthi, Yann Humeau, Jean Pieters |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | PLoS Biology, Vol 12, Iss 3, p e1001820 (2014) |
| Druh dokumentu: | article |
| ISSN: | 1544-9173 1545-7885 |
| DOI: | 10.1371/journal.pbio.1001820 |
| Popis: | Cognitive and behavioral disorders are thought to be a result of neuronal dysfunction, but the underlying molecular defects remain largely unknown. An important signaling pathway involved in the regulation of neuronal function is the cyclic AMP/Protein kinase A pathway. We here show an essential role for coronin 1, which is encoded in a genomic region associated with neurobehavioral dysfunction, in the modulation of cyclic AMP/PKA signaling. We found that coronin 1 is specifically expressed in excitatory but not inhibitory neurons and that coronin 1 deficiency results in loss of excitatory synapses and severe neurobehavioral disabilities, including reduced anxiety, social deficits, increased aggression, and learning defects. Electrophysiological analysis of excitatory synaptic transmission in amygdala revealed that coronin 1 was essential for cyclic-AMP-protein kinase A-dependent presynaptic plasticity. We further show that upon cell surface stimulation, coronin 1 interacted with the G protein subtype Gαs to stimulate the cAMP/PKA pathway. The absence of coronin 1 or expression of coronin 1 mutants unable to interact with Gαs resulted in a marked reduction in cAMP signaling. Strikingly, synaptic plasticity and behavioral defects of coronin 1-deficient mice were restored by in vivo infusion of a membrane-permeable cAMP analogue. Together these results identify coronin 1 as being important for cognition and behavior through its activity in promoting cAMP/PKA-dependent synaptic plasticity and may open novel avenues for the dissection of signal transduction pathways involved in neurobehavioral processes. |
| Databáze: | Directory of Open Access Journals |
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