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Semaphorin 3A Binds to the Perineuronal Nets via Chondroitin Sulfate Type E Motifs in Rodent Brains

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タイトル: Semaphorin 3A Binds to the Perineuronal Nets via Chondroitin Sulfate Type E Motifs in Rodent Brains
著者: Dick, Gunnar 著作を一覧する
Tan, Chin Lik 著作を一覧する
Alves, Joao Nuno 著作を一覧する
Ehlert, Erich M. E. 著作を一覧する
Miller, Gregory M. 著作を一覧する
Hsieh-Wilson, Linda C. 著作を一覧する
Sugahara, Kazuyuki 著作を一覧する
Oosterhof, Arie 著作を一覧する
van Kuppevelt, Toin H. 著作を一覧する
Verhaagen, Joost 著作を一覧する
Fawcett, James W. 著作を一覧する
Kwok, Jessica C. F. 著作を一覧する
キーワード: Chondroitin Sulfate
Neuronal Plasticity
Perineuronal nets
発行日: 2013年 9月20日
出版者: American Society for Biochemistry and Molecular Biology (ASBMB)
誌名: Journal of Biological Chemistry
巻: 288
号: 38
開始ページ: 27384
終了ページ: 27395
出版社 DOI: 10.1074/jbc.M111.310029
抄録: Chondroitin sulfate (CS) and the CS-rich extracellular matrix structures called perineuronal nets (PNNs) restrict plasticity and regeneration in the CNS. Plasticity is enhanced by chondroitinase ABC treatment that removes CS from its core protein in the chondroitin sulfate proteoglycans or by preventing the formation of PNNs, suggesting that chondroitin sulfate proteoglycans in the PNNs control plasticity. Recently, we have shown that semaphorin3A (Sema3A), a repulsive axon guidance molecule, localizes to the PNNs and is removed by chondroitinase ABC treatment (Vo, T., Carulli, D., Ehlert, E. M., Kwok, J. C., Dick, G., Mecollari, V., Moloney, E. B., Neufeld, G., de Winter, F., Fawcett, J. W., and Verhaagen, J. (2013) Mol. Cell. Neurosci. 56C, 186–200). Sema3A is therefore a candidate for a PNN effector in controlling plasticity. Here, we characterize the interaction of Sema3A with CS of the PNNs. Recombinant Sema3A interacts with CS type E (CS-E), and this interaction is involved in the binding of Sema3A to rat brain-derived PNN glycosaminoglycans, as demonstrated by the use of CS-E blocking antibody GD3G7. In addition, we investigate the release of endogenous Sema3A from rat brain by biochemical and enzymatic extractions. Our results confirm the interaction of Sema3A with CS-E containing glycosaminoglycans in the dense extracellular matrix of rat brain. We also demonstrate that the combination of Sema3A and PNN GAGs is a potent inhibitor of axon growth, and this inhibition is reduced by the CS-E blocking antibody. In conclusion, Sema3A binding to CS-E in the PNNs may be a mechanism whereby PNNs restrict growth and plasticity and may represent a possible point of intervention to facilitate neuronal plasticity.
Rights: This research was originally published in Journal of Biological Chemistry. Gunnar Dick, Chin Lik Tan, Joao Nuno Alves, Erich M. E. Ehlert, Gregory M. Miller, Linda C. Hsieh-Wilson, Kazuyuki Sugahara, Arie Oosterhof, Toin H. van Kuppevelt, Joost Verhaagen, James W. Fawcett, and Jessica C. F. Kwok. Semaphorin 3A Binds to the Perineuronal Nets via Chondroitin Sulfate Type E Motifs in Rodent Brains. Journal of Biological Chemistry. 2013; Vol:288(38) p27384–27395. © the American Society for Biochemistry and Molecular Biology
資料タイプ: article
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 菅原 一幸


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