In summary, our cell biological experiments demonstrate that the mammalian cornichon homologue CNIH-2 has an evolutionarily preserved function as a cargo exporter promoting COPII-dependent export from the ER. Interaction with AMPARs, however, significantly extends the physiological role of CNIH-2: while still exploiting CNIH-2 as a cargo exporter for adjustment of imbalances in splice form-dependent trafficking, AMPARs wrest CNIH-2 from its cycle between ER and Golgi complex and integrate them into their functional complexes on the cell surface. Thus, they commandeer CNIH-2 for use as a bona fide auxiliary subunit.
