Cornichon Proteins Determine the Subunit Composition of Synaptic AMPA Receptors
Copyright policy )Cornichon Proteins Determine the Subunit Composition of Synaptic AMPA Receptors
Cornichon-2 and cornichon-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 CNIH-3 conditional knockout 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 kinetics of AMPARs in neurons lacking CNIH-2/-3 are faster than those in WT neurons due to the fast kinetics of GluA2A3 heteromers. The remarkably selective effect of CNIHs on the GluA1 subunit is probably mediated by TARP γ-8, which prevents a functional association of CNIHs with non-GluA1 subunits. These results point to a sophisticated interplay between CNIHs and γ-8 that dictates subunit-specific AMPAR trafficking and the strength and kinetics of synaptic AMPAR-mediated transmission.
- University of California, San Francisco United States
- National Institutes of Health United States
- Ajou University Korea (Republic of)
- National Institute of Neurological Disorders and Stroke United States
- National Institute of Health Pakistan
Cells, Knockout, Neuroscience(all), Hippocampus, Synaptic Transmission, Mice, Organ Culture Techniques, Receptors, AMPA, Psychology, Animals, Receptors, AMPA, Cells, Cultured, Mice, Knockout, Cultured, Neurology & Neurosurgery, Biomedical and Clinical Sciences, Neurosciences, Excitatory Postsynaptic Potentials, Newborn, Protein Subunits, Animals, Newborn, Neurological, Synapses, Biological psychology, Cognitive Sciences
Cells, Knockout, Neuroscience(all), Hippocampus, Synaptic Transmission, Mice, Organ Culture Techniques, Receptors, AMPA, Psychology, Animals, Receptors, AMPA, Cells, Cultured, Mice, Knockout, Cultured, Neurology & Neurosurgery, Biomedical and Clinical Sciences, Neurosciences, Excitatory Postsynaptic Potentials, Newborn, Protein Subunits, Animals, Newborn, Neurological, Synapses, Biological psychology, Cognitive Sciences
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