Fig. 5. A model depicting the role of differentially targeted OGT isoforms in glycan-dependent signaling. The studies described here suggest that transcription from the OGT gene and subsequent alternative splicing produces a number of isoforms including mOGT and ncOGT. The unique N-termini of these isoforms lead to segregation of mOGT into the mitochondrial membrane and targeting of ncOGT to the nucleus and cytoplasm. The hexosamine-signaling pathway is known to modulate the levels of UDP-GlcNAc in response to nutrients (glucose, glutamine, free fatty acids). The UDP-GlcNAc would then be used by each of the uniquely targeted OGT isoforms to modify different intracellular substrates. In the mitochondrion, mOGT may play a role in apoptosis and lipid and carbohydrate metabolism (see text). In the nucleus and cytosol, ncOGT is envisioned to mediate effects on translation, nuclear transport and transcriptional repression.

Return to article