title: Polysialic acid profiles of mice expressing variant allelic combinations of the polysialyltransferases ST8SiaII and ST8SiaIV.
abstract: The post-translational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) represents a remarkable example of dynamic modulation of homo- and heterophilic cell interactions by glycosylation. The synthesis of this unique carbohydrate polymer depends on the polysialyltransferases ST8SiaII and ST8SiaIV. Aiming to understand in more detail the contributions of ST8SiaII and ST8SiaIV to polySia biosynthesis in vivo, we used mutant mouse lines that differ in the number of functional polysialyltransferase alleles. The 1,2-diamino-4,5-methylenedioxybenzene method was used to qualitatively and quantitatively assess the polySia patterns. Similar to the wild-type genotype, long polySia chains (>50 residues) were detected in all genotypes expressing at least one functional polysialyltransferase allele. However, variant allelic combinations resulted in distinct alterations in the total amount of poly-Sia; the relative abundance of long, medium, and short polymers; and the ratio of polysialylated to non-polysialylated NCAM. In ST8SiaII-null mice, 45% of the brain NCAM was non-polysialylated, whereas a single functional allele of ST8SiaII was sufficient to polysialylate approximately 90% of the NCAM pool. Our data reveal a complex polysialylation pattern and show that, under in vivo conditions, the coordinated action of ST8SiaII and ST8SiaIV is crucial to fine-tune the amount and structure of polySia on NCAM.
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, University of Giessen, D-35392 Giessen, Germany.
authors.forename: Sebastian P
authors.initials: SP
authors.lastname: Galuska
authors.forename: Imke
authors.initials: I
authors.lastname: Oltmann-Norden
authors.forename: Hildegard
authors.initials: H
authors.lastname: Geyer
authors.forename: Birgit
authors.initials: B
authors.lastname: Weinhold
authors.forename: Klaus
authors.initials: K
authors.lastname: Kuchelmeister
authors.forename: Herbert
authors.initials: H
authors.lastname: Hildebrandt
authors.forename: Rita
authors.initials: R
authors.lastname: Gerardy-Schahn
authors.forename: Rudolf
authors.initials: R
authors.lastname: Geyer
authors.forename: Martina
authors.initials: M
authors.lastname: Mühlenhoff
mesh_terms: D000483:Alleles; D000818:Animals; D001921:Brain / Q000378:metabolism; D019002:CD56 Antigen / Q000502:physiology*; D014644:Genetic Variation; D005838:Genotype; D006031:Glycosylation; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D011108:Polymers / Q000737:chemistry; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism*; D012799:Sialyltransferases / Q000737:chemistry / Q000235:genetics*
chemical_list: D019002:CD56 Antigen; C501063:Ncam1 protein, mouse; D011108:Polymers; D012794:Sialic Acids; C021319:polysialic acid; C046778:CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase; D012799:Sialyltransferases; C515117:ST8SIA4 protein, human