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Science 326 (5952): 592-596

Copyright © 2009 by the American Association for the Advancement of Science

PTP{sigma} Is a Receptor for Chondroitin Sulfate Proteoglycan, an Inhibitor of Neural Regeneration

Yingjie Shen,1,* Alan P. Tenney,1,*,{dagger} Sarah A. Busch,2 Kevin P. Horn,2 Fernando X. Cuascut,2 Kai Liu,3 Zhigang He,3 Jerry Silver,2 John G. Flanagan1,{ddagger}

Abstract: Chondroitin sulfate proteoglycans (CSPGs) present a barrier to axon regeneration. However, no specific receptor for the inhibitory effect of CSPGs has been identified. We showed that a transmembrane protein tyrosine phosphatase, PTP{sigma}, binds with high affinity to neural CSPGs. Binding involves the chondroitin sulfate chains and a specific site on the first immunoglobulin-like domain of PTP{sigma}. In culture, PTP{sigma}–/– neurons show reduced inhibition by CSPG. A PTP{sigma} fusion protein probe can detect cognate ligands that are up-regulated specifically at neural lesion sites. After spinal cord injury, PTP{sigma} gene disruption enhanced the ability of axons to penetrate regions containing CSPG. These results indicate that PTP{sigma} can act as a receptor for CSPGs and may provide new therapeutic approaches to neural regeneration.

1 Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
2 Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106, USA.
3 Division of Neuroscience, Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

* These authors contributed equally to this work.

{dagger}Present address: Motor Neuron Center, Columbia University, New York, NY 10032, USA.

{ddagger} To whom correspondence should be addressed. E-mail: flanagan{at}hms.harvard.edu

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