Self-regulation of MGAT4A and MGAT4B activity toward glycoproteins through interaction of lectin domain with their own -glycans.

-Acetylglucosaminyltransferases-IVa (GnT-IVa or MGAT4A) and -IVb (MGAT4B) are glycosyltransferase isozymes synthesizing the β1,4-GlcNAc branch in -glycans, a glycan structure involved in diabetes. These enzymes uniquely have a non-catalytic lectin domain, which selectively recognizes the GnT-IV product -glycan branch, but the role of this lectin domain has remained unclear. Here, using UDP-Glo enzyme assays, we discovered that this domain is required for activity toward glycoprotein substrates but not toward free glycans.

Examination of differential glycoprotein preferences of N-acetylglucosaminyltransferase-IV isozymes a and b.

The N-glycans attached to proteins contain various GlcNAc branches, the aberrant formation of which correlates with various diseases. N-Acetylglucosaminyltransferase-IVa (GnT-IVa or MGAT4A) and Gnt-IVb (or MGAT4B) are isoenzymes that catalyze the formation of the β1,4-GlcNAc branch in N-glycans. However, the functional differences between these isozymes remain unresolved.

Discovery of a lectin domain that regulates enzyme activity in mouse N-acetylglucosaminyltransferase-IVa (MGAT4A).

N-Glycosylation is a common post-translational modification, and the number of GlcNAc branches in N-glycans impacts glycoprotein functions. N-Acetylglucosaminyltransferase-IVa (GnT-IVa, also designated as MGAT4A) forms a β1-4 GlcNAc branch on the α1-3 mannose arm in N-glycans. Downregulation or loss of GnT-IVa causes diabetic phenotypes by dysregulating glucose transporter-2 in pancreatic β-cells.

Early-onset schizophrenia and dopamine-related gene polymorphism.

Schizophrenic patients with an onset before age 16 years (early-onset schizophrenia, EOS) would be a rare but attractive subpopulation for genetic studies. This study explored the relationship between the polymorphism of four dopamine-regulating-enzymes (tyrosine hydroxylase, dopamine-beta-hydroxylase, catechol-O-methyltransferase, monoamine oxidase-A) genes, four dopamine-receptors (dopamine D1, D2, D3, D4 receptors) genes and susceptibility to EOS in a Japanese sample. Subjects comprised 51 Japanese patients who met DSM-IV criteria for schizophrenia with an onset before age 16 (by age 15) and 148 Japanese healthy controls.