Developmental changes in the expression of glycogenes and the content of N-glycans in the mouse cerebral cortex
Developmental changes in the expression of glycogenes and the content of N-glycans in the mouse cerebral cortex
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DOI：
10.1093/glycob/cwl076
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发表时间：
2007-03-01
期刊：
影响因子：
4.3
通讯作者：
Ikenaka, Kazuhiro
中科院分区：
文献类型：
--
作者：
Ishii, Akihiro;Ikeda, Takeshi;Ikenaka, Kazuhiro
N-聚糖的生物合成在组织之间显著变化，并且在组织内在空间和时间上受到严格调节。负责控制N-聚糖合成的严格分子机制在很大程度上仍然未知。我们建立了互补脱氧核糖核酸（cDNA）宏阵列系统，分析了发育和成年小鼠大脑皮层中140多种糖基转移酶和糖苷酶的基因表达水平。我们还分析了大脑皮层中存在的主要N-聚糖的相对量，并研究了N-聚糖的合成如何通过这些基因的表达来调节。我们证明了N-连接寡糖的含量在大脑发育过程中发生了显着变化。其中一些变化不能用相应基因表达的改变来解释。例如，早期胚胎脑中核心岩藻糖基化糖链的数量和岩藻糖基转移酶VIII（已知唯一负责核心岩藻糖基化的基因）的表达水平没有成比例地改变。这一结果表明，该基因的转录后调控在调节其酶活性中起着重要作用。另一方面，随着β 1，3-半乳糖基转移酶信使核糖核酸（mRNA）水平的增加，含β 1，3-半乳糖残基的糖链的量在出生后增加。此外，含有LewisX-BA-2的具有外部岩藻糖残基的糖链的数量与梭酰基转移酶IX mRNA的表达密切相关。这些发现增加了我们对负责大脑皮层中N-聚糖生物合成调节的分子机制的理解。
Biosynthesis of N-glycans varies significantly among tissues and is strictly regulated spatially and temporally within the tissue. The strict molecular mechanisms that are responsible for control of N-glycan synthesis remain largely unknown. We developed complementary deoxyribonucleic acid (cDNA) macroarray system and analyzed gene expression levels of more than 140 glycosyltransferases and glycosidases in the cerebral cortex from developing and adult mice. We also analyzed the relative amounts of major N-glycans present in the cerebral cortex and examined how the synthesis of N-glycans might be regulated through the expression of these genes. We demonstrated that the content of N-linked oligosaccharides dramatically changed during the course of brain development. Some of these changes could not be explained by alterations in the expression of the corresponding genes. For example, the amount of core fucosylated sugar chains in the early embryonic brain and the expression level of fucosyltransferase VIII, the only gene known to be responsible for core fucosylation, did not change proportionately. This result suggests that post-transcriptional regulation of this gene plays an important role in regulating its enzymatic activity. On the other hand, the amount of beta 1,3-galactose residue-containing sugar chains increased postnatally following an increase in the level of beta 1,3-galactosyltransferase messenger ribonucleic acid (mRNA). Furthermore, the amount of sugar chains with an outer fucose residue, containing LewisX-BA-2, correlated well with the expression of fusocyltransferase IX mRNA. These findings add to our understanding of the molecular mechanisms responsible for the regulation of N-glycan biosynthesis in the cerebral cortex.