Differential Biosynthesis of Polysialic Acid on Neural Cell Adhesion Molecule (NCAM) and Oligosaccharide Acceptors by Three Distinct α2,8-Sialyltransferases, ST8Sia IV (PST), ST8Sia II (STX), and ST8Sia III

Angata, Kiyohiko; Suzuki, Misa; McAuliffe, Joseph C.; Ding, Yili; Hindsgaul, Ole; Fukuda, Minoru

doi:10.1074/jbc.m910204199

Cited by 103 publications

(104 citation statements)

References 51 publications

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“…1, A-C). However, in contrast to in vitro studies showing that cooperation between ST8SiaII and ST8SiaIV markedly increases polymer length (41), no significant differences in polySia chain length were detectable in vivo. The maximal chain length (determined in five independent experiments for each genotype) was calculated to be 57 Ϯ 1.6 residues for wild-type mice, 55 Ϯ 1.1 residues for ST8SiaIV knock-out mice, and 53 Ϯ 1.9 residues for ST8SiaII knock-out mice.…”

Section: St8siaivcontrasting

confidence: 39%

“…This was not confirmed in vivo because, in wildtype mice, both enzymes together did not yield significantly longer polymers, and the total polySia level was not higher than the sum of polySia found in the two single knock-out mice. Most important, although independent in vitro studies identified ST8SiaII to be less efficient in polySia synthesis compared with ST8SiaIV (12,21,22,41), the most striking changes in NCAM polysialylation in vivo were found to be due to ST8SiaII deficiency. Lack of ST8SiaIV did not change the total polySia level, whereas loss of ST8SiaII resulted in a reduction by 39% accompanied by an altered chain length distribution and an increase in non-polysialylated NCAM from 0 to 45%.…”

Section: Discussionmentioning

confidence: 99%

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Polysialic Acid Profiles of Mice Expressing Variant Allelic Combinations of the Polysialyltransferases ST8SiaII and ST8SiaIV

Galuska¹,

Oltmann-Norden²,

Geyer³

et al. 2006

J. Biol. Chem.

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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 polySia; 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 ϳ90% 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.Carbohydrate modifications of proteins and lipids play an important role in the development and maintenance of the nervous system as mediators of cell recognition events (1). One striking example is polysialic acid (polySia), 2 a linear homopolymer of ␣2,8-linked N-acetylneuraminic acid. In vertebrates, polySia is found almost exclusively as a post-translational modification of the neural cell adhesion molecule (NCAM), a member of the immunoglobulin superfamily. Attachment of polySia to NCAM was demonstrated to double the hydrodynamic radius of NCAM, thereby increasing the intermembrane space and disrupting the adhesive properties of NCAM and other cell adhesion molecules such as L1, integrins, and cadherins (2-4). PolySia promotes migration of neuronal precursor cells, axonal outgrowth, and synaptic plasticity (for review, see Ref. 5). In addition to its function as a negative regulator of cell adhesion, polySia was shown to bind heparan sulfate proteoglycans (6), forming a complex that supports synaptogenesis and activity-dependent remodeling of synapses (7). In addition, polySia can bind brain-derived neurotrophic factor to enhance brain-derived neurotrophic factor-dependent survival of cortical neurons (8, 9) and appears to be involved in the regulation of neurotransmitter receptor activity (10). Whereas polySia levels are high during embryonic development, expression in the adult is restricted to brain areas of persistent neurogenesis and synaptic plasticity (11).Interestingly, the biosynthesis of polySia depends on two enzymes, the Golgi-resident polysialyltransferases ST8SiaII and ST8SiaIV, which s...

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Section: St8siaivcontrasting

confidence: 39%

Section: Discussionmentioning

confidence: 99%

Polysialic Acid Profiles of Mice Expressing Variant Allelic Combinations of the Polysialyltransferases ST8SiaII and ST8SiaIV

Galuska¹,

Oltmann-Norden²,

Geyer³

et al. 2006

J. Biol. Chem.

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“…However, ST8SIA2 has been found to associate with both schizophrenia and bipolar disorder in one recent study using genomewide microsatellite scan, 29 implying that ST8SIA2 may lie in a common pathway for the development of bipolar and schizophrenia. It is a polysialytransferase, which modulates the function of neural cell adhesion molecule 1 (NCAM1) by catalyzing the transfer of transferpolysialic acid 30 to NCAM1. NCAM1 has an important role during the development of the central nervous system and also has been shown to associate with bipolar disorder in a previous study.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study of bipolar I disorder in the Han Chinese population

et al. 2010

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We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 a-Nacetyl-neuraminide a-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with Pvalues of 4.87 Â 10 À7 (rs2709736) and 6.05 Â 10 À6 (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P = 9.74 Â 10 À6 ) and in CACNB2 (Calcium channel, voltage-dependent, b-2 subunit) gene (rs11013860, P = 5.15 Â 10 À5 ), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P = 6.55 Â 10 À5 and P = 1.48 Â 10 À5 , respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.

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“…In the MZ͞layer 1, the neural cell adhesion molecule is preferentially polysialylated, and this polysialylation attenuates the adhesive property of the neural cell adhesion molecule, thereby facilitating neural cell migration (2,33). Polysialylation requires the preceding ␣2,3-or ␣2,6-linked sialylation reaction (34). Siat7e and Siat9 are ␣2,6-and ␣2,3-sialyltransferases, respectively (35).…”

Section: Discussionmentioning

confidence: 99%

Distinct ontogenic and regional expressions of newly identified Cajal-Retzius cell-specific genes during neocorticogenesis

Yamazaki

Sekiguchi

Takamatsu

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Cajal-Retzius (CR) cells are early-generated transient neurons and are important in the regulation of cortical neuronal migration and cortical laminar formation. Molecular entities characterizing the CR cell identity, however, remain largely elusive. We purified mouse cortical CR cells expressing GFP to homogeneity by fluorescenceactivated cell sorting and examined a genomewide expression profile of cortical CR cells at embryonic and postnatal periods. We identified 49 genes that exceeded hybridization signals by >10-fold in CR cells compared with non-CR cells at embryonic day 13.5, postnatal day 2, or both. Among these CR cell-specific genes, 25 genes, including the CR cell marker genes such as the reelin and calretinin genes, are selectively and highly expressed in both embryonic and postnatal CR cells. These genes, which encode generic properties of CR cell specificity, are eminently characterized as modulatory composites of voltage-dependent calcium channels and sets of functionally related cellular components involved in cell migration, adhesion, and neurite extension. Five genes are highly expressed in CR cells at the early embryonic period and are rapidly down-regulated thereafter. Furthermore, some of these genes have been shown to mark two distinctly different focal regions corresponding to the CR cell origins. At the late prenatal and postnatal periods, 19 genes are selectively up-regulated in CR cells. These genes include functional molecules implicated in synaptic transmission and modulation. CR cells thus strikingly change their cellular phenotypes during cortical development and play a pivotal role in both corticogenesis and cortical circuit maturation.

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Differential Biosynthesis of Polysialic Acid on Neural Cell Adhesion Molecule (NCAM) and Oligosaccharide Acceptors by Three Distinct α2,8-Sialyltransferases, ST8Sia IV (PST), ST8Sia II (STX), and ST8Sia III

Cited by 103 publications

References 51 publications

Polysialic Acid Profiles of Mice Expressing Variant Allelic Combinations of the Polysialyltransferases ST8SiaII and ST8SiaIV

Polysialic Acid Profiles of Mice Expressing Variant Allelic Combinations of the Polysialyltransferases ST8SiaII and ST8SiaIV

Genome-wide association study of bipolar I disorder in the Han Chinese population

Distinct ontogenic and regional expressions of newly identified Cajal-Retzius cell-specific genes during neocorticogenesis

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