Cornichon Proteins Determine the Subunit Composition of Synaptic AMPA Receptors

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• 作者：Bruce E. Herring¹ ; ⁵ ; Yun Shi¹ ; ⁵ ; Young Ho Suh³ ; ^{suhy@ajou.ac.kr} ; Chan-Ying Zheng⁴ ; Sabine M. Blankenship¹ ; Katherine W. Roche⁴ ; Roger A. Nicoll¹ ; ² ; ^{roger.nicoll@ucsf.edu}
• 刊名：Neuron
• 出版年：2013
• 出版时间：20 March, 2013
• 年：2013
• 卷：77
• 期：6
• 页码：1083-1096
• 全文大小：3284 K

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Summary

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 ¦Ã-8, which prevents a functional association of CNIHs with non-GluA1 subunits. These results point to?a sophisticated interplay between CNIHs and ¦Ã-8 that dictates subunit-specific AMPAR trafficking and the strength and kinetics of synaptic AMPAR-mediated transmission.