Regulated expression and neural functions of human natural killer-1 (HNK-1) carbohydrate

Abstract

Human natural killer-1 (HNK-1) carbohydrate, comprising a unique trisaccharide HSO(3)-3GlcAβ1-3Galβ1-4GlcNAc, shows well-regulated expression and unique functions in the nervous system. Recent studies have revealed sophisticated and complicated expression mechanisms for HNK-1 glycan. Activities of biosynthetic enzymes are controlled through the formation of enzyme-complexes and regulation of subcellular localization. Functional aspects of HNK-1 carbohydrate were examined by overexpression, knockdown, and knockout studies of these enzymes. HNK-1 is involved in several neural functions such as synaptic plasticity, learning and memory, and the underlying molecular mechanisms have been illustrated upon identification of the target carrier glycoproteins of HNK-1 such as the glutamate receptor subunit GluA2 or tenascin-R. In this review, we describe recent findings about HNK-1 carbohydrate that provide further insights into the mechanism of its expression and function in the nervous system.

Clinical and Immunological Features of Opsoclonus-Myoclonus Syndrome in the Era of Neuronal Cell Surface Antibodies

“…47,48 In brain, HNK-1 is present not only in MAG but also in several proteins such as cell adhesion molecules, tenascins, and integrins widely present in the brain. 49,50 These proteins as well as the HNK-1-containing GluR2 subunit of AMPAR, which was precipitated with the CSF of our patients, are involved in synaptic plasticity and a variety of neuronal functions. 20 …”

Perineuronal nets labeled by monoclonal antibody VC1.1 ensheath interneurons expressing parvalbumin and calbindin in the rat amygdala

“…The VC1.1 antibody recognizes an N-linked carbohydrate epitope associated with integral membrane proteins that is either identical to or highly overlaps the carbohydrate epitope labeled by the HNK-1 antibody (Arimatsu et al, 1987; Kosaka et al, 1990; Naegele and Barnstable, 1991; Barnstable et al, 1992). This VC1.1/HNK-1 carbohydrate epitope has been shown to be a sulfated trisaccharide that has a unique terminal sulfated glucuronic acid (Kizuka and Oka, 2012). It is carried by several extracellular matrix components including myelin associated glycoproteins (95-105 kDa band), N-CAMs (145 kDa and 170 kDa bands), some aggrecan proteoglycans (650-700 kDa bands), and tenascin–R (Arimatsu et al, 1987; Zaremba et al, 1990; Naegele and Barnstable, 1991; Barnstable et al, 1992; Matthews et al, 2002).…”

Molecular Basis of the Receptor Interactions of Polysialic Acid (polySia), polySia Mimetics, and Sulfated Polysaccharides

“…In addition to the family of negatively charged sialic acids and their polymers or mimicking molecules, sulfated carbohydrates like the HNK‐1 epitope play important roles as contact points on neuronal cells. In addition, the HNK‐1 carbohydrate regulates migration of neural crest cells, synaptic plasticity, learning and memory, and preferential motor reinnervation . When sulfated carbohydrates from marine organisms (e.g., algae) that express many different sulfated glycans can be identified which act in a similar manner to the HNK‐1 glycan, this may identify an important source from which such bioactive molecules can be obtained.…”