Glycobiology of the synapse: the role of glycans in the formation,maturation, and modulation of synapses

Synapses, which are the fundamental functional unit of the nervous system, are considered to be highly specialized cell adhesion structures. Studies since the 1960s demonstrated that various carbohydrates and glycoproteins are expressed in synapses in the central and peripheral nervous system. Although the functional roles of these synaptic carbohydrates and glycoproteins remain to be determined, rapidly accumulating data suggest that they may play critical roles in the formation, maturation, and functional modulation of synapses.     

Glycobiology of the synapse: the role of glycans in the formation,maturation, and modulation of synapses

Synapses, which are the fundamental functional unit of the nervous system, are considered to be highly specialized cell adhesion structures. Studies since the 1960s demonstrated that various carbohydrates and glycoproteins are expressed in synapses in the central and peripheral nervous system. Although the functional roles of these synaptic carbohydrates and glycoproteins remain to be determined, rapidly accumulating data suggest that they may play critical roles in the formation, maturation, and functional modulation of synapses.     

糖生物学

糖生物学是近年来迅速发展的一门新兴前沿分支学科,简单介绍了糖生物学的现状及其发展趋势和展望。     

Glycobiology of the neuromuscular junction

Most molecules that are present at synapses are glycosylated with carbohydrates, and some carbohydrate structures are themselves uniquely synaptic in their localization. Thus, proteins or lipids at the synapse may bear distinct carbohydrates that alter their localization or function. Here, I will review the evidence that there are unique synaptic carbohydrates at the neuromuscular junction. Then, I will review the evidence that such carbohydrates can affect the function of synaptic proteins, with particular attention to agrin, dystroglycan, and the neural cell adhesion molecule (NCAM). Finally, I will review recent data that demonstrates a role for one carbohydrate structure, the cytotoxic T cell (CT) antigen, in neuromuscular development. These studies suggest that glycosylation is an important modification to consider in studies of synapse formation and function.     

Glycobiology in medicine

Glycoconjugates play important roles in biological reactions (for example sialyl Lewis^x in homing of leukocytes and mannose-6-phosphate in targeting of lysosomal enzymes) and thus aberration in carbohydrate structures in glyco-conjugates can lead to abnormal biological behaviors. In fact, glycoconjugates expressed on the surfaces of tumor and cancer cells are considerably different from those of the normal cells, at least quantitatively. There are many known carbohydrate-deficient glycoprotein syndromes. As recognition of carbohydrate groups is mostly performed by carbohydrate-binding proteins, aberration in these proteins also results in disease status (for example I-cell disease). Many pathogens use carbohydrates as recognition markers for invasion (examples are influenza virus and cholera toxin). The carbohydrate receptors in various organs can be used for targeting drugs, antibodies and even DNAs. Conjugation of polysaccharides derived from pathogenic micro-organisms with appropriate proteins provides effective vaccines against the micro-organisms.     

Glycobiology of fertilization in the pig

By adopting internal fertilization, the meeting of both gametes - the sperm and the egg - and thus the highly coordinated sequence of interactions leading to fertilization, occur in the female reproductive tract. In mammals, the oviduct has been shown to translate the requirements of the female, coordinating sperm activation (capacitation) and sperm transport with the arrival of the ovulated egg. A hierarchy of carbohydrate-based interactions accompanies these events ranging from the binding of uncapacitated sperm to the oviductal epithelium (establishment of the female sperm reservoir), to the primary and secondary binding processes contributing to gamete recognition and sperm penetration of the oocyte zona pellucida. The current perspective will focus on the carbohydrate-recognition systems in the binding events during fertilization in the pig. The roles of the major carbohydrate-binding proteins, the spermadhesins and the acrosomal serine proteinase, pro/acrosin are discussed under consideration of recent structural data. The glycans and the glycoproteins of the porcine oviduct with a focus on the candidate sperm receptors as well as the zona pellucida N-glycans of prepuberal pigs have been characterized by a mass spectrometric approach. Furthermore, some preliminary data supporting the hypothesis that the zona pellucida has to undergo a maturation process during oocyte development are presented.     

Glycobiology of Plasmodium falciparum

The human malaria parasite, Plasmodium falciparum, has as its only glycoconjugate GPI anchors. These structures, present in essentially all parasite surface proteins, are associated with disease pathology. In contrast, the parasite depends for essential recognition events on saccharides associated with host cell glycoproteins and proteoglycans.     

糖生物学和糖组学

糖生物学和糖组学,虽然都是研究糖类在机体中的作用,但是,它们分别有不同的视角。糖生物学是沿袭了糖化学、糖生物化学发展而来,着重研究糖类和蛋白质的相互作用;而糖组学则源于基因组学,以基因编码糖基转移酶为起始,由这些酶得到糖组,进而开展糖组的研究。     

Glycobiology of neuromuscular disorders

There has been a recent explosion in the identification of neuromuscular diseases caused by mutations in genes that affect carbohydrate metabolism or protein glycosylation. A number of these findings relate to defects in the glycosylation of alpha dystroglycan. Alpha dystroglycan is an essential component of the dystrophin-glycoprotein complex, and aberrant glycosylation of alpha dystroglycan is associated with multiple forms of muscular dystrophy in mice and humans. We review the evidence that defects in dystroglycan glycosylation cause muscular dystrophy. In addition, we review evidence that glycobiology is important in other disorders that affect muscle, including hereditary inclusion body myopathy type II and congenital disorders of glycosylation. Finally, we discuss the long-term potential of glycotherapies for muscle disorders.     

Glycobiology of human milk

Glycans are characteristic components of milk, and each species has unique patterns of specific carbohydrates. Human milk is unusually rich in glycans, with the major components being lactose and oligosaccharides, representing approximately 6.8 and 1% of the milk, respectively. Other sources of glycans in human milk include monosaccharides, mucins, glycosaminoglycans, glycoproteins, glycopeptides, and glycolipids. In human milk, the presence and patterns of these glycans vary depending upon the stage of lactation and the maternal genes and their genetic polymorphisms that control glycosyl transferases. The synthesis of milk glycans utilizes a significant portion of the metabolic energy that the mother expends when producing her milk, but other than lactose, these glycans contribute little to the nutritional needs of the infant. The data herein support several functions. 1) Many human milk glycans inhibit pathogens from binding to the intestinal mucosa. 2) Human milk glycans attenuate inflammation. 3) Glycans also directly stimulate the growth of beneficial (mutualist) bacteria of the microbiota (formerly considered commensal microflora of the intestine); these mutualists and their fermentation products can, in turn, (a) inhibit pathogens, (b) modulate signaling and inflammation, and (c) the fermentation products can be absorbed and utilized as a source of dietary calories. These functions can help direct and support intestinal postnatal growth, development, and ontogeny of colonization. The many functions of the milk glycans may synergistically protect infants from disease. Hence, human milk glycans and their homologs may serve as novel prophylactic or therapeutic agents for a diverse range of deleterious conditions.     

丝状真菌糖生物学

蛋白质的糖基化修饰是一种保守的真核生物蛋白质翻译后修饰,存在于从酵母到人的所有真核生物中,赋予了蛋白质功能的多样性。目前对蛋白质糖基化修饰的了解主要来源于对酵母和哺乳动物细胞的研究,但单细胞真核生物或动物细胞水平的研究,很难反映糖基化修饰在多细胞真核生物的发育分化过程中的复杂功能。由于丝状真菌是多细胞真核生物,有相对简单的发育分化过程,因而是研究多细胞真核生物糖基化功能的理想模型之一,在过去10年中,丝状真菌的糖生物学研究开始受到重视,目前的研究结果表明糖基化修饰与丝状真菌的生长、发育密切相关。     

植物糖生物学研究进展

自1988年糖生物学概念提出以来, 国内外科学家在动物、微生物领域取得了大量的研究成果, 但植物糖生物学的研究进展较慢, 目前少见系统的专著或综述。该文围绕植物正常生长时糖信号、逆境时糖信号、糖蛋白及其糖链、重要糖基转移酶及植物凝集素等植物糖生物学的主要问题, 全面阐述植物糖生物学的各个研究分支, 并介绍各领域的最新研究进展。提出了植物糖生物学的概念, 并将其定义为研究植物与糖类互作机制及植物体内糖(糖链与糖分子)结构及生物学功能的科学。     

植物糖生物学研究进展

自1988年糖生物学概念提出以来,国内外科学家在动物、微生物领域取得了大量的研究成果,但植物糖生物学的研究进展较慢,目前少见系统的专著或综述。该文围绕植物正常生长时糖信号、逆境时糖信号、糖蛋白及其糖链、重要糖基转移酶及植物凝集素等植物糖生物学的主要问题,全面阐述植物糖生物学的各个研究分支,并介绍各领域的最新研究进展。提出了植物糖生物学的概念,并将其定义为研究植物与糖类互作机制及植物体内糖（糖链与糖分子）结构及生物学功能的科学。