Schematic of N-glycan branching and receptor dynamics at the cell surface.

Oligosaccharyltransferase (OST) substitutes NXS/T sites of proteins in the rough endoplasmic reticulum (RER), transferring the pre-assembled glycan from Glc3Man9GlcNAc2-pp-dolichol to the Asn. Glycoproteins traffic to the Golgi where the N-glycans are remodeled, and the structural details depend on enzyme expression and UDP-GlcNAc supply. The branching enzymes Mgat1, Mgat2, Mgat4, and Mgat5 differ in Km values for UDP-GlcNAc “D” and for glycoprotein acceptor “A”. The pathway has evolved for pathway ultrasensitivity to UDP-GlcNAc. The epitopes are completed in the trans-Golgi (small box) where efficient substitution with Gal generates the LacNAc epitope, and can be extended by poly-LacNAc. Further extension with galactose generates epitopes for galectin binding, with effects on receptor dynamics, interactions and trafficking.