title: Protective effects of polysialic acid on proteolytic cleavage of FGF2 and proBDNF/BDNF.
abstract: Polysialic acid (polySia) is a linear polymer of sialic acid that modifies neural cell adhesion molecule (NCAM) in the vertebrate brain. PolySia is a large and exclusive molecule that functions as a negative regulator of cell-cell interactions. Recently, we demonstrated that polySia can specifically bind fibroblast growth factor 2 (FGF2) and BDNF; however, the protective effects of polySia on the proteolytic cleavage of these proteins remain unknown, although heparin/heparan sulfate has been shown to impair the cleavage of FGF2 by trypsin. Here, we analyzed the protective effects of polySia on the proteolytic cleavage of FGF2 and proBDNF/BDNF. We found that polySia protected intact FGF2 from tryptic activity via the specific binding of extended polySia chains on NCAM to FGF2. Oligo/polySia also functioned to impair the processing of proBDNF by plasmin via binding of oligo/polySia chains on NCAM. In addition, the polySia structure synthesized by mutated polysialyltransferase, ST8SIA2/STX(SNP7), which was previously identified from a schizophrenia patient, was impaired for these functions compared with polySia produced by normal ST8SIA2. Taken together, these data suggest that the protective effects of polySia toward FGF2 and proBDNF may be involved in the regulation of the concentrations of these neurologically active molecules.
authors.affiliation: Bioscience and Biotechnology Center School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Hane
authors.affiliation: Bioscience and Biotechnology Center School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Matsuoka
authors.affiliation: Bioscience and Biotechnology Center.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Ono
authors.affiliation: Bioscience and Biotechnology Center.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miyata
authors.affiliation: Bioscience and Biotechnology Center.
authors.forename: Ken
authors.initials: K
authors.lastname: Kitajima
authors.affiliation: Bioscience and Biotechnology Center chi@agr.nagoya-u.ac.jp.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sato
mesh_terms: D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry*; D005341:Fibrinolysin / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D011498:Protein Precursors / Q000737:chemistry*; D059748:Proteolysis; D012794:Sialic Acids / Q000737:chemistry*; D014357:Trypsin / Q000737:chemistry
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011498:Protein Precursors; D012794:Sialic Acids; C021319:polysialic acid; D016222:Fibroblast Growth Factor 2; C579455:BDNF protein, human; D014357:Trypsin; D005341:Fibrinolysin
keywords: BDNF; FGF2; NCAM; SPR; ST8SIA2/STX; Trypsin; plasmin; polysialic acid; polysialyltransferase; proBDNF