Department of Developmental Neuroscience, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo, 183-8526, Japan.
Neurochem Res. 2011 Jul;36(7):1228-40. doi: 10.1007/s11064-010-0324-y. Epub 2010 Nov 26.
Chondroitin sulfate and heparan sulfate proteoglycans are major components of the cell surface and extracellular matrix in the brain. Both chondroitin sulfate and heparan sulfate are unbranched highly sulfated polysaccharides composed of repeating disaccharide units of glucuronic acid and N-acetylgalactosamine, and glucuronic acid and N-acetylglucosamine, respectively. During their biosynthesis in the Golgi apparatus, these glycosaminoglycans are highly modified by sulfation and C5 epimerization of glucuronic acid, leading to diverse heterogeneity in structure. Their structures are strictly regulated in a cell type-specific manner during development partly by the expression control of various glycosaminoglycan-modifying enzymes. It has been considered that specific combinations of glycosaminoglycan-modifying enzymes generate specific functional microdomains in the glycosaminoglycan chains, which bind selectively with various growth factors, morphogens, axon guidance molecules and extracellular matrix proteins. Recent studies have begun to reveal that the molecular interactions mediated by such glycosaminoglycan microdomains play critical roles in the various signaling pathways essential for the development of the brain.
硫酸软骨素和硫酸乙酰肝素蛋白聚糖是大脑细胞表面和细胞外基质的主要成分。硫酸软骨素和硫酸乙酰肝素都是未分支的高度硫酸化多糖，分别由葡萄糖醛酸和 N-乙酰半乳糖胺、以及葡萄糖醛酸和 N-乙酰葡萄糖胺重复二糖单位组成。在高尔基器中进行生物合成时，这些糖胺聚糖通过葡萄糖醛酸的硫酸化和 C5 差向异构化高度修饰，导致结构的多样性。它们的结构在发育过程中以细胞类型特异性的方式受到严格调控，部分原因是各种糖胺聚糖修饰酶的表达控制。人们认为，糖胺聚糖修饰酶的特定组合在糖胺聚糖链中产生特定的功能微区，这些微区与各种生长因子、形态发生素、轴突导向分子和细胞外基质蛋白选择性结合。最近的研究开始揭示，这种糖胺聚糖微区介导的分子相互作用在大脑发育所必需的各种信号通路中发挥着关键作用。
