Gangliosides of the Vertebrate Nervous System.
Gangliosides of the Vertebrate Nervous System.
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脊椎动物神经系统的神经节苷脂。
DOI：
10.1016/j.jmb.2016.05.020
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发表时间：
2016-08-14
影响因子：
5.6
通讯作者：
Schnaar RL
中科院分区：
文献类型：
--
作者：
Schnaar RL
神经节苷脂是脊椎动物细胞和组织中存在的唾液酸鞘糖脂，是脊椎动物神经细胞表面的主要分子决定因素。由附着在神经酰胺脂类上的唾液酸聚糖组成，相同的四种结构-GM1、GD1a、GD1b和GT1b-代表了所有哺乳动物和鸟类大脑中绝大多数(90%)的神经节苷脂。神经节苷脂主要存在于细胞膜的外表面，糖链朝向外，神经节苷脂与神经节苷脂、神经鞘蛋白、胆固醇和脂筏中的精选蛋白--质膜的动态功能亚域--相互联系。神经节苷脂生物合成基因的先天突变揭示了神经节苷脂在人类神经系统中的功能。ST3GAL5是脑神经节苷脂生物合成早期的一种酶的编码基因，它的突变会导致早发性癫痫，并伴有严重的运动和认知衰退，而编码较晚步骤的基因B4GALNT1的突变会导致遗传性痉挛截瘫并伴有智力缺陷。脑神经节苷脂的分子功能包括通过侧向(Cis)结合调节同一膜上的受体，以及通过与对面细胞上的神经节苷脂结合蛋白的反式相互作用调节细胞-细胞识别。神经节苷脂还影响Aβ(阿尔茨海默病)和α-突触核蛋白(帕金森病)的聚集。随着分析、生化和遗传学工具的发展，对神经节苷脂的研究有望揭示神经和神经胶质细胞分化、神经元兴奋性、神经系统损伤后轴突生长以及神经退行性疾病中蛋白质折叠的分子控制机制。
Gangliosides, sialylated glycosphingolipids found on all vertebrate cells and tissues, are major molecular determinants on the surfaces of vertebrate nerve cells. Comprised of a sialylated glycan attached to a ceramide lipid, the same four structures – GM1, GD1a, GD1b and GT1b – represent the vast majority (>90%) of gangliosides in the brains of all mammals and birds. Primarily found on the outer surface of the plasma membrane with their glycans facing outward, gangliosides associate laterally with each other, sphingomyelin, cholesterol, and select proteins in lipid rafts – dynamic functional subdomains of the plasma membrane. The functions of gangliosides in the human nervous system are revealed by congenital mutations in ganglioside biosynthetic genes. Mutations in ST3GAL5, which codes for an enzyme early in brain ganglioside biosynthesis, results in an early-onset seizure disorder with profound motor and cognitive decay, whereas mutations in B4GALNT1, a gene encoding a later step, result in hereditary spastic paraplegia accompanied by intellectual deficits. The molecular functions of brain gangliosides include regulation of receptors in the same membrane via lateral (cis) associations and regulation of cell-cell recognition by trans interaction with ganglioside binding proteins on apposing cells. Gangliosides also affect aggregation of Aβ (Alzheimer’s disease) and α-synuclein (Parkinson’s Disease). As analytical, biochemical and genetic tools advance, research on gangliosides promises to reveal mechanisms of molecular control related to nerve and glial cell differentiation, neuronal excitability, axon outgrowth after nervous system injury, and protein folding in neurodegenerative diseases.