open access

https://hdl.handle.net/2115/62910

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

英語

Perineuronal nets

2013-09-20

American Society for Biochemistry and Molecular Biology (ASBMB)

Journal of Biological Chemistry

288(38)

27384-27395

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.

学術雑誌論文

Version of Record

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 viaChondroitin 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

0021-9258

1083-351X