Coronin 1 Regulates Cognition and Behavior through Modulation of cAMP/Protein Kinase A Signaling
PLoS Biol. 2014-03-25; 12(3): e1001820
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1. PLoS Biol. 2014 Mar 25;12(3):e1001820. doi: 10.1371/journal.pbio.1001820.
eCollection 2014 Mar.
Coronin 1 regulates cognition and behavior through modulation of cAMP/protein
kinase A signaling.
Jayachandran R(1), Liu X(1), Bosedasgupta S(1), Müller P(1), Zhang CL(2), Moshous
D(3), Studer V(1), Schneider J(4), Genoud C(5), Fossoud C(6), Gambino F(2),
Khelfaoui M(2), Müller C(7), Bartholdi D(8), Rossez H(1), Stiess M(1), Houbaert
X(2), Jaussi R(9), Frey D(9), Kammerer RA(9), Deupi X(10), de Villartay JP(3),
Lüthi A(7), Humeau Y(2), Pieters J(1).
(1)Biozentrum, University of Basel, Basel, Switzerland.
(2)Interdisciplinary Institute for Neuroscience, Bordeaux, France.
(3)Hospital Necker, Paris, France.
(4)Department of Radiology, University Children Hospital, UKBB, Basel,
(5)Center for Cellular Imaging and NanoAnalytics, University of Basel, Basel,
Switzerland; Friedrich Miescher Institute, Basel, Switzerland.
(6)Centre Hospitalier Universitaire de Nice, Nice, France.
(7)Friedrich Miescher Institute, Basel, Switzerland.
(8)University Hospital Basel, Basel, Switzerland.
(9)Biomolecular Research Laboratory, Paul Scherrer Institute, Villigen,
(10)Biomolecular Research Laboratory, Paul Scherrer Institute, Villigen,
Switzerland; Condensed Matter Theory, Paul Scherrer Institute, Villigen,
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.
PMID: 24667537 [Indexed for MEDLINE]
Conflict of interest statement: The authors have declared that no competing