Regulation of HNK-1 (Human Natural Killer-1) Carbohydrate Expression: Multiple Control Mechanisms of Biosynthetic Enzyme Activity

HNK-1 carbohydrate is highly expressed in the nervous system and is involved in higher-order brain functions such as learning and memory. HNK-1 has a unique structure with sulfated glucuronic acid attached to the non-reducing end of N-acetyllactosamine (HSO₃-3GlcA β1-3Gal β1-4GlcNAc-). Two glucuronyltransferases and a sulfotransferase play key roles in its biosynthesis. We focused on how these enzyme activities are regulated in terms of HNK-1 expression. We revealed that the transferases form a hetero-complex for the efficient biosynthesis and that the activity is regulated by well-controlled intracellular localization. These facts indicate that HNK-1 expression is strictly regulated through multiple control mechanisms of the biosynthetic enzyme activity.