CNIH-1 has been assigned not simply a facilitating but a regulatory role on ER export of TGF-α, crucially depending on its expression level [27]. Immature TGF-α was prevented from anterograde traffic by high expression levels of CNIH-1. The authors explained their finding by preferential interaction of CNIH-1 with the less glycosylated forms of TGF-α, while implying a definite localization of CNIH-1 in the early secretory pathway. Intriguingly, we also found less complex glycosylation of GluA2i when co-expressed with CNIH-2. However, those immature receptors were not retained in the ER as might be expected, but reached the plasma membrane efficiently. We did also not observe any negative effect on GluA surface expression when increasing the cDNA transfection ratio of CNIH-2:GluA2i (data not shown). Hence, we interpret our results on GluA maturation by sterical hindrance that is imposed on putative N-glycosylation sites in the glutamate receptor by its interaction with the extracellular loop of CNIH-2 [16]. Whether this is of physiological relevance for AMPAR stability on the cell surface or for their biophysical properties, e.g. their ligand affinity [47], needs to be investigated.
