Glycobiology of the Nervous System

Yasuhiko Kizuka, Kenji Kanekiyo, Shinobu Kitazume, Naoyuki Taniguchi, Kizuka, Yasuhiko, Kanekiyo, Kenji, Kitazume, Shinobu, Taniguchi, Naoyuki

In the nervous system, various unique glycans not found in other tissues are expressed on glycoproteins, and their expression/functions have been studied using specific antibodies/lectins. Among brain-specific glycans in mammals, we focus on human natural killer-1 (HNK-1) and related Cat-315 epitopes, which can be detected using specific antibodies. It is known that the HNK-1 epitope is expressed on N- and O-mannosylated glycans and that Cat-315 mAb preferentially recognizes the HNK-1 epitope on brain-specific "branched O-mannose glycan." The β1,6-branched O-mannose structure is synthesized by a brain-specific glycosyltransferase, N-acetylglucosaminyltransferase-IX (GnT-IX, also designated as GnT-Vb). Using GnT-IX gene-deficient mice and specific antibodies/lectins, the function of GnT-IX was found to be quite different from that of its ubiquitous homologue, GnT-V. Using Cat-315 mAb, the receptor protein tyrosine phosphatase-beta (RPTPβ) was identified as an in vivo target glycoprotein for GnT-IX. Analysis of the function of branched O-mannose glycan on RPTPβ indicated that its loss promoted the recovery process after myelin injury (called remyelination) in brain and that this phenomenon is probably caused in vivo by reduced activation of astrocytes in GnT-IX-deficient brain.