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Carbohydrate diversity of chondroitin sulfate proteoglycans and its functional specificity in retinotectal pathway formation

硫酸软骨素蛋白多糖的碳水化合物多样性及其在视网膜顶盖通路形成中的功能特异性

基本信息

批准号：
16500191
负责人：
ICHIJO Hiroyuki
金额：
$ 2.37万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Chondroitin sulfates (CSs) are carbohydrate polymers consisting of disaccharide units of glucuronic acid and N-acetylgalactosamine. Depending on sulfation positions, different units are distinguished, and combinations of the various CSs' units demonstrate structural diversity. Although CSs are known to be involved in inhibition of axonal growth, it has not been shown that their inhibitions are direct effect, or that their structural diversity is related to differential effects.MO-225 monoclonal antibody recognizes particular structural motifs in CSs. To know CSs structure recognized by MO-225, polystyrene beads were coated with preparations of CSs in which particular units are enriched. Binding MO-225 to the CSs coated polystyrene beads were examined by using fluorocytometry ; MO-225 preferentially bound to the CSs rich in C, D, and E unit.Immunohistochemical analyses in chick embryos revealed that MO-225 recognized that (1)neuropil encircling the optic tract and (2)outer surface of the retinal axons running in an interface layer between the optic tract and its encircling neuropil. The results suggest that the CSs recognized by MO-225 containing C,D, or E unit in rich are involved with setting up boundary of the optic tract and chronological sorting of the retinal axons in the optic tract.To know effects of the CSs particularly recognized by MO-225, behaviors of retinal growth cones have been examined during their encounter on the beads coated with the CSs rich in C,D, or E unit. CSs rich in C or D unit were not likely to induce considerable effects on the retinal growth cones. Other types of CSs are presently being examined.

硫酸软骨素（CSs）是由葡萄糖醛酸和n -乙酰半乳糖胺的双糖单位组成的碳水化合物聚合物。根据硫化位置的不同，可以区分出不同的单位，并且各种CSs单位的组合显示出结构的多样性。虽然已知CSs参与抑制轴突生长，但尚未表明它们的抑制是直接作用，或者它们的结构多样性与差异作用有关。MO-225单克隆抗体识别CSs中的特定结构基序。为了了解MO-225识别的CSs结构，在聚苯乙烯珠上涂覆了富含特定单元的CSs制剂。用荧光细胞法检测MO-225与CSs包被聚苯乙烯珠的结合；MO-225优先与富含C、D和E单元的CSs结合。鸡胚免疫组化分析显示，MO-225能够识别(1)环绕视神经束的神经瘤和(2)视神经束与其环绕神经瘤之间的界面层中运行的视网膜轴突的外表面。结果表明，含有丰富C、D或E单元的MO-225识别的CSs参与了视神经束边界的建立和视神经束内视网膜轴突的时间排序。为了了解MO-225识别的CSs的作用，研究了视网膜生长锥在涂有富含C、D或E单位的CSs的珠子上遇到时的行为。富含C或D单位的CSs不太可能对视网膜生长锥产生显著影响。目前正在研究其他类型的CSs。