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Between neurodevelopmental disorders and normal brain formation: Focusing on neuronal differentiation and migration as key milestones.

開催日 2014/9/13
時間 9:00 - 11:00
会場 Room F(302)
Chairperson(s) 川内 健史 / Takeshi Kawauchi (慶應義塾大学医学部生理学教室 / PRESTO, JST / Department of Physiology, Keio University School of Medicine, Japan)
小山 隆太 / Ryuta Koyama (東京大学大学院薬学系研究科薬品作用学教室 / Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan)

Roles of glycosaminoglycans in neuronal development

  • S3-F-1-2
  • 北川 裕之 / Hiroshi Kitagawa:1 
  • 1:神戸薬大・生化 / Dept Biochem, Kobe Pharmaceutical Univ, Kobe, Japan 

Extracellular factors that surround cell surfaces play essential roles in a wide spectrum of neurobiological functions, including neuronal development and neuronal plasticity. Glycans are ubiquitous throughout the extracellular and pericellular spaces, and they may function as microenvironmental cues during neuronal development and remodeling. Recent advances in the field of glyco-neuroscience clearly indicate that distinct glycans, especially sulfated glycosaminoglycan (GAG) chains, are functionally relevant to neuronal plasticity. GAGs are linear polysaccharides that consist of repetitive disaccharide units comprised of an amino sugar, either N-acetylgalactosamine or N-acetylglucosamine, and a glucuronic acid (1). Despite their simplified polysaccharide backbones, GAGs acquire remarkable structural variability via further enzymatic modifications, which is the primary reason for their functional diversity (1). During brain development, sulfation profiles, defined as the 4-sulfation/6-sulfation (4S/6S) ratio, of chondroitin sulfate (CS), a representative sulfated GAG, change dramatically. The developmental increase in 4S/6S ratio is tightly coupled to the termination of the critical period for ocular dominance plasticity (2). Notably, systemic overexpression of human C6ST-1, a sulfotransferase responsible for the 6-sulfation of CS chains, in mice shows a substantially lower 4S/6S ratio and the mice retain juvenile level of the cortical plasticity even in adulthood (2). In addition to the variable sulfation status of GAG chains, the chain length and/or the number of GAG chains per core protein are also finely tuned under the control of GAG biosynthetic machineries. Here, I will present recent data regarding the importance of GAG chains in neural development.

1. Mikami, T., and Kitagawa, H. (2013) Biosynthesis and function of chondroitin sulfate. Biochim. Biophys. Acta 1830, 4719-4733.
2. Miyata, S., Komatsu, Y., Yoshimura, Y., Taya, C., and Kitagawa, H. (2012) Persistent cortical plasticity by upregulation of chondroitin 6-sulfation. Nature Neurosci. 15, 414-422.

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