Structural and functional impairments of polysialic acid (polySia)-neural cell adhesion molecule (NCAM) synthesized by a mutated polysialyltransferase of a schizophrenic patient

Polysialic acid (polySia) is a homopolymer of sialic acid with a degree of polymerization (DP) of 8–400. When present on neural cell adhesion molecule (NCAM), polySia has anti-adhesive effects on cell–cell interactions owing to its bulky polyanionic nature, and is involved in the regulation of neurogenesis and neuronal functions. Recently, we demonstrated that polySia functions not only as an anti-cell adhesion molecule, but also as a reservoir scaffold for brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF2), which are biologically active molecules in neurogenesis. To understand the significance of polySia structure in the reservoir function, we focused on polySia-NCAM biosynthesized by mutated polysialyltransferase (ST8SiaII or STX) that was reported in a schizophrenia patient. The polySia-NCAM biosynthesized by mutant ST8SiaII/STX contained less polySia with shorter chain length and exhibited impaired reservoir function for BDNF and FGF2 as compared with that synthesized by wild-type (wt) ST8SiaII/STX. Our findings suggest that the quantity and quality of polySia on NCAM are important for normal neuronal functioning.