Chunk #19 — DISCUSSION — Variations in N-glycan types and contents in the two MOPR variants may play a role in region-specific effects of A112G on MOPR protein expression
N-glycosylation plays an important role in correct folding of receptors in the endoplasmic reticulum, and hence, their sorting from the endoplasmic reticulum to the plasma membrane. N-glycosylation thereby affects receptor expression [for example, (Fan et al., 1997; Zhang et al., 2001; Li et al., 2007)]. Recently we found that A112G led to reduced MOPR N-glycosylation in the mouse brain (Huang et al., 2012). Similarly, A118G decreased N-glycosylation of the human MOPR expressed in cultured cells and in addition, compromised stability of the human MOPR protein (Huang et al., 2012). If the changes in MOPR protein stability by the SNP are uniform, MOPR levels will be reduced similarly in all the brain regions. However, we found that MOPR levels were lower in some, but not all, brain regions of G/G mice. This may be attributed to variations in N-glycan types and contents in the MOPR in different brain regions. Importantly, the wild-type MOPR has been shown to be differentially modified by N-linked glycans in the CPu and thalamus of the rat and mouse, suggesting that N-glycosylation of MOPR is brain region-specific
