Figure 7. Model of an inherent Golgi self-correcting mechanism to maintain LacNAc homeostasis.
The majority of UDP-GlcNAc entering the Golgi is supplied to its early compartments by the UDP-GlcNAc/UMP antiporters, which are preferentially localized to the cis/medial Golgi. Under branching proficient conditions (A), UDP-GlcNAc is used by the branching enzymes MGAT1, 2, 4, and 5, with little unused UDP-GlcNAc supplying the poly-LacNAc synthesizing B3GNT enzymes. The resulting array of N-glycans produced thus contains more LacNAc branches than linear LacNAc polymers (A). When the branching pathway is disrupted (B), or presumably the Golgi is otherwise stressed, leading to reduced UDP-GlcNAc usage in the medial Golgi, UDP-GlcNAc is driven forward (at least partially through intercisternal tubules) and promotes production of bioequivalent poly-LacNAc containing glycans by the trans Golgi-resident B3GNT family of enzymes. Under this scenario, loss of LacNAc branches is balanced by increased production of linear LacNAc polymers, a self-correcting ability that serves to maintain cell surface LacNAc density and thus the galectin-glycoprotein lattice (A). In the context of T cells, this homeostatic mechanism acts to curtail catastrophic T cell hyperactivity and promotes self-tolerance.