Regulation and Function of Sulfoglucuronyl (HNK-1) Carbohydrate in Developing Nervous System
Many of the biological functions of the SGC may be mediated by a receptor or SGC-binding protein (i.e., acting as a lectin). We isolated and purified from brain a 30 kDa SGC-binding protein, SBP-1, which specifically bound to SGC of SGGLs and SGC-glycoproteins in vitro, suggesting that SBP-1 may act as a receptor for SGC in vivo. In embryonic cerebral cortex, SBP-1 was strongly expressed in the proliferating neurons of the ventricular zone and migrating neurons through the intermediate zone, and subplate and settled neurons of the cortical plate. In early posnatal cerebellum, SBP-1 was strongly expressed in the proliferating granule neurons of the external granule cell layers (EGCL), migrating neurons through the molecular layer and settled neurons of the internal granule cell layer (IGCL). The expression of SBP-1 in neurons of these regions declined after the cell migration was complete. The expression of SGC was not in neuronal cell bodies, but it appeared to be in neuronal and/or glial processes surrounding the neurons. This expression of SGC declined similar to SBP-1 and disappeared after the neuronal migration was complete. Thus, the expressions of SBP-1 and SGC were developmentally regulated and appeared to be chronologically co-ordinated with neuronal migration and maturation. SBP-1, expressed on cell-surfaces of migrating immature neurons, recognizes and interacts with SGC localized on apposing neuronal and/or glial processes. Once the SBP-1 expressing neurons reach their appropriate targets, the expression of both SBP-1 and SGC is down regulated allowing further differentiation. This hypothesis was supported by in vitro experiments with the dissociated cortical neurons as well as explant cultures and live thick slices of neonatal cerebellum. Anti-SGC (HNK-1) and anti-SBP-1 antibodies and sulfoglucuronyl glycolipid, SGGL specifically and severely reduced neurite outgrowth and cell migration in dose dependent manners. SBP-1-SGC interactions provide potential mechanism for guidance and cell signaling, in the processes of neuronal migration and terminal differentiation.