Functions of chondroitin sulfate/dermatan sulfate chains in brain development: Critical roles of E and iE disaccharide units recognized by a single chain antibody GD3G7.

Purushothaman, Anurag; Fukuda, Junko; Mizumoto, Shuji; ten Dam, Gerdy B.; van Kuppevelt, Toin H.; Kitagawa, Hiroshi; Mikami, Tadahisa; Sugahara, Kazuyuki

Functions of chondroitin sulfate/dermatan sulfate chains in brain development: Critical roles of E and iE disaccharide units recognized by a single chain antibody GD3G7.

Purushothaman, Anurag; Fukuda, Junko; Mizumoto, Shuji et al.

Journal of Biological Chemistry, 2007, 282(27), 19442-19452

Permalink : https://hdl.handle.net/2115/28126

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アクセス権	open access
URI	https://hdl.handle.net/2115/28126
タイトル	Functions of chondroitin sulfate/dermatan sulfate chains in brain development: Critical roles of E and iE disaccharide units recognized by a single chain antibody GD3G7.
著者	Purushothaman, Anurag ; Fukuda, Junko ; Mizumoto, Shuji ; ten Dam, Gerdy B. ; van Kuppevelt, Toin H. ; Kitagawa, Hiroshi ; Mikami, Tadahisa ; Sugahara, Kazuyuki
著者名 Purushothaman, Anurag
著者名 Fukuda, Junko
著者名 Mizumoto, Shuji
著者名 ten Dam, Gerdy B.
著者名 van Kuppevelt, Toin H.
著者名 Kitagawa, Hiroshi
著者名 Mikami, Tadahisa
e-Rad_Researcher 60154449 著者名 Sugahara, Kazuyuki 菅原, 一幸
言語	英語
発行日	2007-07-06
出版者	American Society for Biochemistry and Molecular Biology
収録物名	Journal of Biological Chemistry
巻(号)	282(27)
ページ	19442-19452
抄録	Chondroitin sulfate (CS) and dermatan sulfate (DS) have been implicated in the processes of neural development in the brain. In this study, we characterized developmentally regulated brain CS/DS chains using a single chain antibody, GD3G7, produced by the phage display technique. Evaluation of the specificity of GD3G7 toward various glycosaminoglycan preparations showed that this antibody specifically reacted with squid CS-E (rich in the GlcUA1–3GalNAc(4,6-O-sulfate) disaccharide unit E), hagfish CS-H (rich in the IdoUA1–3GalNAc(4,6-O-sulfate) unit iE), and shark skin DS (rich in both E and iE units). In situ hybridization for the expression of N-acetylgalac-tosamine-4-sulfate 6-O-sulfotransferase in the postnatal mouse brain, which is involved in the biosynthesis of CS/DS-E, showed a widespread expression of the transcript in the developing brain except at postnatal day 7, where strong expression was observed in the external granule cell layer in the cerebellum. The expression switched from the external to internal granule cell layer with development. Immunohistochemical localization of GD3G7 in the mouse brain showed that the epitope was relatively abundant in the cerebellum, hippocampus, and olfactory bulb. GD3G7 suppressed the growth of neurites in embryonic hippocampal neurons mediated by CS-E, suggesting that the epitope is embedded in the neurite outgrowth-promoting motif of CS-E. In addition, a CS-E decasaccharide fraction was found to be the critical minimal structure needed for recognition by GD3G7. Four discrete decasaccharide epitopic sequences were identified. The antibody GD3G7 has broad applications in investigations of CS/DS chains during the central nervous system's development and under various pathological conditions.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Copyright © 2007 by the American Society for Biochemistry and Molecular Biology.
PISSN	0021-9258
EISSN	1083-351X
関連情報	PMID 17500059
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1074/jbc.M700630200