Altered protein expression of galactose and N-acetylgalactosamine transferases in schizophrenia superior temporal gyrus

Abnormal glycosylation in schizophrenia brain has been previously implicated in disruptions to protein trafficking, localization, and function. Glycosylation is an enzyme-mediated posttranslational modification and, along with reports of altered glycan biosynthesis and abnormal glycan levels in peripheral fluids, growing evidence for altered glycosylation pathway activity in schizophrenia prompted investigation of specific enzymes which may be responsible for these abnormalities. Glycosylation is a highly variable yet tightly controlled cellular process and, depending on the molecule(s) affected, altered glycan modifications can influence the trajectory of many key functional pathways. In a preliminary gene array study, abnormal transcript expression of 36 glycosylation-associated enzymes was identified in schizophrenia brain. Subsequently, protein expression abnormalities of enzymes which act on glucose (UGGT2), mannose (EDEM2), fucose (FUT8, POFUT2), and N-acetylglucosamine (MGAT4A, B3GNT8) have been reported in this illness. The current study investigates protein expression levels by western blot analysis of the galactose and N-acetylgalactosamine (GalNAc) transferases B3GALTL1, B4GALT1, C1GALT1, GALNT2, GALNT7, GALNT16, and GALNTL5, as well as a related chaperone protein, COSMC, in superior temporal gyrus of age- and sex-matched pairs of schizophrenia and non-psychiatrically ill comparison subjects (N = 16 pairs). In schizophrenia, reduced β-1,4-galactosyltransferase 1 (B4GALT1) and polypeptide GalNAc-transferase 16 (GALNT16) were identified. These findings add support to the hypothesis that dysregulated glycosylation-associated enzyme expression contributes to altered protein glycosylation and downstream substrate-specific defects in schizophrenia.