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Chunk #34 — DISCUSSION — A model for the interaction between γ-8 and CNIH with AMPAR subunits — GluA2A3 heteromers

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Cornichon proteins determine the subunit composition of synaptic AMPA receptors.
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In GluA1 KO mice the remaining GluA2A3 receptors bind to γ-8 and have a high IKA/IGlu ratio indicating that they also contain 4 γ-8 (Figure S4C and D). The fast kinetics of native neuronal GluA2A3 receptors in GluA1 conditional KO mice (Figure 4E), the inability of CNIH-2 knock-down to influence AMPA EPSCs of neurons from GluA1 KO mice (Figure 3E and S4B) and the failure of neuronal GluA2A3 receptors to coimmunoprecipitate CNIH-2 (Figure 3I) argue that CNIH is prevented from associating with these receptors. Thus we assert that GluA2A3 receptors contain 4 γ-8 and 0 CNIH molecules (Figure 8D). While speculative, given the likelihood that γ-8 inhibits the interaction of CNIH on GluA2 subunits, we believe γ-8 may similarly inhibit CNIH interaction with GluA3.