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Glycobiology Advance Access originally published online on September 16, 2008
Glycobiology 2008 18(12):1044-1053; doi:10.1093/glycob/cwn084
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Direct binding of polysialic acid to a brain-derived neurotrophic factor depends on the degree of polymerization

Yukihiro Kanato, Ken Kitajima and Chihiro Sato1

Graduate School of Bioagricultural Sciences and Bioscience and Biotechnology Center, Nagoya University, Nagoya 464-8601, Japan

1 To whom correspondence should be addressed: Tel: +81-52-789-4295; Fax: +81-52-789-5228; e-mail: chi{at}agr.nagoya-u.ac.jp

Received on July 9, 2008; revised on August 30, 2008; accepted on September 2, 2008

Polysialic acid (polySia) is the homopolymer of sialic acid and negatively regulates neuronal cell–cell and cell–extracellular matrix interactions through steric and repulsive hindrance due to its bulky polyanionic structure. Whether polySia also functions as a positive regulator in the nervous system through binding to specific ligands is not known. In the present study, we demonstrated that a brain-derived neurotrophic factor (BDNF) dimer binds directly to polySia to form a large complex with an Mr greater than 2000 kDa under physiologic conditions. Although somewhat affected by the linkage and type of sialic acid components in the polySia, the complex formation is highly dependent on the polySia chain length. The minimum degree of polymerization required for the complex formation is 12. This is the first study to demonstrate the biologic significance of the degree of polySia polymerization in eukaryotes. Similar large polySia complexes form with other neurotrophic factors such as nerve growth factor, neurotrophin-3, and neurotrophin-4. Furthermore, the BDNF, after making a complex with polySia, can bind to the BDNF receptors, TrkB and p75NTR. The complex formation of BDNF with polySia upregulates growth or/and survival of neuroblastoma cells. These findings suggest that polySia functions as a reservoir of BDNF and other neurotrophic factors and may serve to regulate their local concentrations on the cell surface.

Key words: brain-derived neurotrophic factor / NCAM / p75NTR / polysialic acid/TrkB


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