Functions of Chondroitin Sulfate and Heparan Sulfate in the Developing Brain
Functions of Chondroitin Sulfate and Heparan Sulfate in the Developing Brain
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DOI：
10.1007/s11064-010-0324-y
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发表时间：
2011-07-01
影响因子：
4.4
通讯作者：
Kamimura, K.
中科院分区：
文献类型：
--
作者：
Maeda, N.;Ishii, M.;Kamimura, K.
硫酸软骨素和硫酸乙酰肝素蛋白聚糖是脑中细胞表面和细胞外基质的主要组分。硫酸软骨素和硫酸乙酰肝素都是无支链的高度硫酸化多糖，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-乙酰葡糖胺的重复二糖单元组成。在它们在高尔基体中的生物合成期间，这些糖胺聚糖通过葡萄糖醛酸的硫酸化和C5差向异构化而高度修饰，导致结构的多样性异质性。它们的结构在发育过程中以细胞类型特异性方式受到严格调控，部分受各种糖胺聚糖修饰酶的表达控制。已经认为，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结构域，其选择性地与各种生长因子、形态发生素、轴突引导分子和细胞外基质蛋白结合。最近的研究已经开始揭示，由这种糖胺聚糖微结构域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起着关键作用。
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.