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Coronin 1 Regulates Cognition and Behavior through Modulation of cAMP/Protein Kinase A Signaling

Jayachandran, Rajesh and Liu, Xiaolong and Bosedasgupta, Somdeb and Müller, Philipp and Zhang, Chun-Lei and Moshous, Despina and Studer, Vera and Schneider, Jacques and Genoud, Christel and Fossoud, Catherine and Gambino, Frédéric and Khelfaoui, Malik and Müller, Christian and Bartholdi, Deborah and Rossez, Helene and Stiess, Michael and Houbaert, Xander and Jaussi, Rolf and Frey, Daniel and Kammerer, Richard A. and Deupi, Xavier and de Villartay, Jean-Pierre and Lüthi, Andreas and Humeau, Yann and Pieters, Jean. (2014) Coronin 1 Regulates Cognition and Behavior through Modulation of cAMP/Protein Kinase A Signaling. PLoS Biology, Vol. 12, H. 3 , e1001820. pp. 1-21.

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Official URL: http://edoc.unibas.ch/dok/A6243573

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Abstract

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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Biochemistry (Pieters)
UniBasel Contributors:Pieters, Jean
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Public Library of Science
ISSN:1545-7885
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Mar 2018 14:27
Deposited On:23 May 2014 08:33

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