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Cornichon Proteins Determine the Subunit Composition of Synaptic AMPA Receptors
Abstract:SUMMARYCornichon-2 and -3 (CNIH-2/-3) are AMPA receptor (AMPAR) binding proteins that promote receptor trafficking, and markedly slow AMPAR deactivation in heterologous cells, but their role in neurons is unclear. Using CNIH-2 and -3 conditional knock-out mice, we find a profound reduction of AMPAR synaptic transmission in the hippocampus. This deficit is due to the selective loss of surface GluA1-containing AMPARs (GluA1A2 heteromers), leaving a small residual pool of synaptic GluA2A3 heteromers. The kinetic… Show more
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Cited by 151 publications
(209 citation statements)
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“…Finally, we reasoned that if GSG1L acts on CNIH2 to regulate AMPAR deactivation kinetics, then GSG1L might not have an effect on AMPAR deactivation in neurons lacking CNIH2. In agreement with a previous report 10 , we found that expression of a CNIH2 short hairpin RNA (shRNA) construct that effectively knocked down CNIH2 (ref. 10 ), but not a control scramble shRNA construct, in hippocampal CA1 neurons sped up AMPAR deactivation kinetics ( Fig.…”
Section: Resultssupporting
confidence: 93%
“…In agreement with a previous report 10 , we found that expression of a CNIH2 short hairpin RNA (shRNA) construct that effectively knocked down CNIH2 (ref. 10 ), but not a control scramble shRNA construct, in hippocampal CA1 neurons sped up AMPAR deactivation kinetics ( Fig. 7e and Supplementary Fig.…”
Section: Resultssupporting
confidence: 93%
See 1 more Smart Citation
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD).Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD.The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC).Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
“…Finally, we reasoned that if GSG1L acts on CNIH2 to regulate AMPAR deactivation kinetics, then GSG1L might not have an effect on AMPAR deactivation in neurons lacking CNIH2. In agreement with a previous report 10 , we found that expression of a CNIH2 short hairpin RNA (shRNA) construct that effectively knocked down CNIH2 (ref. 10 ), but not a control scramble shRNA construct, in hippocampal CA1 neurons sped up AMPAR deactivation kinetics ( Fig.…”
Section: Resultssupporting
confidence: 93%
“…In agreement with a previous report 10 , we found that expression of a CNIH2 short hairpin RNA (shRNA) construct that effectively knocked down CNIH2 (ref. 10 ), but not a control scramble shRNA construct, in hippocampal CA1 neurons sped up AMPAR deactivation kinetics ( Fig. 7e and Supplementary Fig.…”
Section: Resultssupporting
confidence: 93%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD).Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD.The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC).Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
“…Our functional experiments, therefore, allowed crude separation and analysis of the individual effects of γ5 and CNIH2 auxiliary subunits on AMPAR function, consistent with previous reports 21 , 22 , 40 .…”
Section: Resultssupporting
confidence: 88%
Modulation of GluA2–γ5 synaptic complex desensitization, polyamine block and antiepileptic perampanel inhibition by auxiliary subunit cornichon-2
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD).Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD.The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC).Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
“…1 and 4 ), suggesting that this effect is unlikely to be subunit-specific and applies to AMPARs in general. These results are consistent with the proposed role of CNIHs as ER chaperones based on their evolutionary origin as ER cargo exporters and their ER-Golgi localization in mammalian cells ( 24 , 26 , 76 ). The loss of CNIH-2 leads to a loss of surface AMPARs ( 23 , 24 , 26 ), and CNIH-2 is well known to promote ER exit of AMPARs ( 21 , 23 , 24 , 25 ).…”
Section: Discussionsupporting
confidence: 90%
“…These results are consistent with the proposed role of CNIHs as ER chaperones based on their evolutionary origin as ER cargo exporters and their ER-Golgi localization in mammalian cells ( 24 , 26 , 76 ). The loss of CNIH-2 leads to a loss of surface AMPARs ( 23 , 24 , 26 ), and CNIH-2 is well known to promote ER exit of AMPARs ( 21 , 23 , 24 , 25 ). Despite the small population of GluA1 homomers, these calcium-permeable GluA1 homomeric receptors are critical in neuronal development, synaptic plasticity, and neurological diseases ( 58 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ).…”
Section: Discussionsupporting
confidence: 90%
Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD).Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD.The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC).Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.
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