HNK-1 Glyco-Epitope: Complex machinery for biosynthesis

The human natural killer-1 (HNK-1) carbohydrate is a well-known glyco-epitope that is predominantly expressed in the central and peripheral nervous systems and plays an essential role in higher brain functions such as synaptic plasticity, spatial learning, and memory. HNK-1 has a unique sulfated trisaccharide structure, HSO3-3GlcAβ1-3Galβ1-4GlcNAc, and is expressed under the control of highly sophisticated machineries that cannot simply be explained by quantitative changes in a single synthetic enzyme, such as the selective expression of this epitope on limited types of proteins. Recent studies investigating the regulation of HNK-1 at cellular and molecular levels demonstrated that HNK-1- synthesizing enzymes physically and functionally interacted with each other to form a heteromeric enzyme complex. This enzyme complex then facilitated the biosynthesis of HNK-1 by increasing production efficacy and has also been implicated in the sorting of carrier molecules. While the biological significance of the enzyme complex in regulating the HNK-1 epitope has begun to be clarified, HNK-1ST also possesses distinct functions independent of the canonical synthesis of HNK-1, which has provided an insight into the diversity of the regulatory mechanisms responsible for mammalian glycosylation.