Cloning and in situ hybridization analysis of the expression of polysialyltransferase mRNA in the developing and adult rat brain

Wood, Graham K.; Liang, Jin Jun; Flores, Gonzalo; Ahmad, Sultan; Quirion, Rémi; Srivastava, Lalit K.

doi:10.1016/s0169-328x(97)00209-x

Cited by 31 publications

(25 citation statements)

References 44 publications

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“…In particular, the expression profile of PST and STX during development and adult tissues suggest that PST and STX are expressed differentially but overlapping in some specific tissues (19,(25)(26)(27)(28). To elucidate the functional difference between PST and STX, in the present study, we first examined the enzymatic activity of these enzymes toward different core glycans of NCAM.…”

Section: Discussionmentioning

confidence: 99%

“…Such a cooperative polysialylation may be the reason why both PST and STX are necessary in places such as the hippocampus where extensive polysialylation is required even in adult. The mossy fibers in the hippocampus originate from the dentate gyrus, which express both PST and STX and contain much more polysialic acid than CA2 region expressing STX alone (19,28). It will be of significance to determine if PST forms larger polysialic acid on NCAM than STX in vivo and if PST and STX function in a cooperative manner in neural cells as well.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies indicate that both PST and STX are highly expressed in early stages of mouse or rat development and that this amount is at a maximum before birth (25)(26)(27)(28). In mouse, 10 days after birth, STX is dramatically decreased while PST is moderately decreased during development (25,27).…”

mentioning

confidence: 99%

“…On the other hand, both PST and STX are present in many of the cells so far examined. For example, polysialic acid in the hippocampus in adult brain appears to be synthesized by concerted actions of PST and STX (19,26,28). These results combined together indicate that PST and STX may individually have distinct functions, but it is not clear why two similar enzymes are expressed in common regions of the brain.…”

mentioning

confidence: 99%

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Differential and Cooperative Polysialylation of the Neural Cell Adhesion Molecule by Two Polysialyltransferases, PST and STX

Angata

Suzuki

Fukuda

1998

Journal of Biological Chemistry

111

108

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PST and STX are polysialyltransferases that form polysialic acid in the neural cell adhesion molecule (NCAM), and these two polysialyltransferases often exist together in the same tissues. To determine the individual and combined roles of PST and STX in polysialic acid synthesis, in the present study we asked if PST and STX differ in the acceptor requirement and if PST and STX act together in polysialylation of NCAM. We first examined whether PST and STX differ in the requirement of sialic acid and core structures of N-glycans attached to NCAM. Polysialic acid was formed well on Lec4 and Lec13 cells, which are defective in N-acetylglucosaminyltransferase V and GDP-fucose synthesis, respectively, demonstrating that a side chain elongating from GlcNAc␤136Man␣136R and ␣-1,6-linked fucose are not required. PST and STX were found to add polysialic acid on NCAM⅐Fc molecules sialylated by ␣-2,3-or ␣-2,6-linkage in vitro, but not on NCAM⅐Fc lacking either sialic acid. These results indicate that both PST and STX have relatively broad specificity on N-glycan core structures in NCAM and no remarkable difference exists between PST and STX for the requirement of core structures and sialic acid attached to the N-glycans of NCAM. We then, using various N-glycosylation site mutants of NCAM, discovered that PST strongly prefer the sixth N-glycosylation site, which is the closest to the transmembrane domain, over the fifth site. STX slightly prefer the sixth N-glycosylation site over the fifth N-glycosylation site. The results also demonstrated that polysialic acid synthesized by PST is larger than that synthesized by STX in vitro. Moreover, a mixture of PST and STX more efficiently synthesized polysialic acid on NCAM than PST or STX alone. These results suggest that polysialylation of NCAM is influenced by the difference between PST and STX in their preference for N-glycosylation sites on NCAM. The results also suggest that PST and STX form polysialylated NCAM in a synergistic manner.Polysialic acid is a developmentally regulated carbohydrate composed of a linear homopolymer of ␣-2,8-linked sialic acid (1). NCAM 1 is highly polysialylated in embryonic tissues. In contrast, the majority of NCAM in adult tissues lacks this unique glycan, but polysialylated NCAM is present in the olfactory bulb and hippocampus of adult brain, where neural regeneration persists (2, 3). There is increasing evidence that polysialylated NCAM promotes cell migration and enhances neurite outgrowth and branching during development and neural regeneration (2-4). Polysialic acid is thought to modulate the functional properties of NCAM by rendering it less adhesive to itself (homophilic binding) (5, 6) or to other cell surface molecules (heterophilic binding). In the latter case, it has been shown that NCAM engages in interactions with L1 on the same membrane (cis-interaction) (7).The studies on NCAM knockout mice demonstrated an abnormal formation in the olfactory bulb and hippocampus and a defect in spatial learning and memory (8, 9). By using NCAM knocko...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Differential and Cooperative Polysialylation of the Neural Cell Adhesion Molecule by Two Polysialyltransferases, PST and STX

Angata

Suzuki

Fukuda

1998

Journal of Biological Chemistry

111

108

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“…The genes encoding both enzymes have been cloned from several species and sequenced (9 -13). The availability of cDNAs encoding these enzymes has facilitated new approaches to study the function, mechanism, and regulation of polysialylation of N-CAM (13)(14)(15)(16). The properties and developmentally regulated expression of polyST activity in the membrane fraction of embryonic chicken (17,18) and rat (19) brain have been studied.…”

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Chemical Analysis of the Developmental Pattern of Polysialylation in Chicken Brain

Inoue

Lin

Inoue

2000

Journal of Biological Chemistry

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Recent studies have demonstrated the involvement of two polysialyltransferases in neural cell adhesion molecule (N-CAM) polysialylation. The availability of cDNAs encoding these enzymes facilitated studies on polysialylation of N-CAM. However, there is a dearth of detailed structural information on the degree of polymerization (DP), DP ranges, and the influence of embryogenesis on the DP. It is also unclear how many polysialic acid (polySia) chains are attached to a single core N-glycan. In this paper we applied new, efficient, and sensitive high pressure liquid chromatography methods to qualitatively and quantitatively analyze the polySia structures expressed on embryonic and adult chicken brain N-CAM. Our studies resulted in the following new findings. 1) The DP of the polySia chains was invariably 40-50 throughout developmental stages from embryonic day 5 to 21 after fertilization. In contrast, glycopeptides containing polySia with shorter DPs, ranging from 15 to 35, were isolated from adult brain. 2) Chemical evidence showed glycan chains abundant in Neu5Ac␣2,8Neu5Ac were expressed during all developmental stages including adult. 3) Levels of both diand polySia were found to show distinctive changes during embryonic development.Polysialic acid (polySia) 1 is a structurally and functionally unique glycotope expressed on the surface of living cells (1). In higher vertebrates, the ␣2,8-linked homopolymer of Neu5Ac is the only reported structure of polySia, although diverse structures of polySia differing in C-5 substitution of Sia residues and in the inter-residue linkages have been discovered in bacteria, invertebrates, and lower vertebrates (2). In embryonic vertebrate brain, the neural cell adhesion molecule (N-CAM) is a major carrier protein of polySia. A hypothesis that the presence of polySia on N-CAM attenuates the adhesive function of this molecule (3, 4) is supported by temporally regulated expression of polySia on embryonic N-CAM, its spatially limited expression in the olfactory bulb, hippocampus, and cerebellum of adult mammalian brain (where continuous plasticity is required). PolySia is also an oncodevelopmental antigen that is re-expressed on a number of human tumors, including neuroblastomas (5) and Wilms tumor (6). The presence of polySia on N-CAM not only functions as a negative regulator of N-CAMmediated homotypic cell-cell adhesion but also decreases interactions with other cells. Although the molecular details of how polySia affects cell interactions has not been fully elucidated, it has been hypothesized to depend on the physical properties of this negatively charged and heavily hydrated polymer (7,8).Recent studies have shown that two polysialyltransferases (polySTs), designated PST-1 (PST/ST8SiaIV) and STX (ST8SiaII), catalyze the polysialylation of N-CAM. The genes encoding both enzymes have been cloned from several species and sequenced (9 -13). The availability of cDNAs encoding these enzymes has facilitated new approaches to study the function, mechanism, and regulation of polysial...

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Regulation of neural cell adhesion molecule polysialylation state by cell-cell contact and protein kinase C delta

2000

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Cloning and in situ hybridization analysis of the expression of polysialyltransferase mRNA in the developing and adult rat brain

Cited by 31 publications

References 44 publications

Differential and Cooperative Polysialylation of the Neural Cell Adhesion Molecule by Two Polysialyltransferases, PST and STX

Differential and Cooperative Polysialylation of the Neural Cell Adhesion Molecule by Two Polysialyltransferases, PST and STX

Chemical Analysis of the Developmental Pattern of Polysialylation in Chicken Brain

Regulation of neural cell adhesion molecule polysialylation state by cell-cell contact and protein kinase C delta

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