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Chunk #41 — DISCUSSION — CNIH-2/-3 promotes forward trafficking of GluA1-containing AMPARs in the ER/Golgi

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Cornichon proteins determine the subunit composition of synaptic AMPA receptors.
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More specifically our results indicate that CNIH is essential for the functional expression of GluA1-containing receptors on the surface. Although, at present, we cannot say at what forward trafficking step of these receptors requires CNIH proteins. It is possible that CNIH proteins are required for the transport of GluA1-containing AMPARs from the ER to the Golgi, from the Golgi to the neuronal surface or both. Future study will undoubtedly be necessary to answer these questions. However, our data would suggest that γ-8 proteins associate with AMPARs prior to CNIH proteins as AMPARs progress through the secretory pathway due to γ-8 seemingly being required for the subunit-specific actions of CNIH proteins on the surface trafficking of GluA1A2 heteromers (Figure 8E).