PTPσ Is a Receptor for Chondroitin Sulfate Proteoglycan, an Inhibitor of Neural Regeneration

By Yingjie Shen, Alan P. Tenney, S. Busch, Kevin P. Horn, Fernando X. Cuascut, Kai-Fenp Liu, Zhigang He, J. Silver, J. Flanagan. Science, 2009

675 citations recorded by the source corpus.

Toward Neuronal Regeneration Neurons in the central nervous system that are severed or crushed do not regenerate well. Part of the problem derives from the glial scars left behind after such damage. The scar tissue contains sulfated proteoglycans that seem to inhibit axon regeneration. Shen et al. (p. 592, published online 15 October) have now identified a protein tyrosine phosphatase (PTP) in mouse neuronal membranes that functions as a receptor for the proteoglycans. Neurons that lacked this particular PTP showed improved regeneration. Regeneration remained incomplete, presumably due to other inhibitory factors in the way of complete axon regeneration. Mouse neurons that lack a receptor for inhibitory proteoglycans show improved regeneration. 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, PTPσ, binds with high affinity to neural CSPGs. Binding involves the chondroitin sulfate chains and a specific site on the first immunoglobulin-like domain of PTPσ. In culture, PTPσ–/– neurons show reduced inhibition by CSPG. A PTPσ fusion protein probe can detect cognate ligands that are up-regulated specifically at neural lesion sites. After spinal cord injury, PTPσ gene disruption enhanced the ability of axons to penetrate regions containing CSPG. These results indicate that PTPσ can act as a receptor for CSPGs and may provide new therapeutic approaches to neural regeneration.

Subfields: Cell Biology, Cellular and Molecular Neuroscience

View Paper: https://www.semanticscholar.org/paper/3214db2dd43ac3631fa084e4478360466069cdad

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In Cellular and Molecular Neuroscience

Citations in the corpus

Rho signaling and axon regeneration. (2012, background): “…s (PTPs) and leukocyte common antigen-related phosphatase have been identified as CSPG receptors, and antagonism of these receptors pharmacologically or through gene disruption promotes axon regeneration (Fisher et al., 2011; Fry, Chagnon, López-Vales, Tremblay, & David, 2009; Shen et al., 2009).”