A new role for RPTPsigma in spinal cord injury: signaling chondroitin sulfate proteoglycan inhibition.
It has been known for more than two decades that chondroitin sulfate proteoglycans (CSPGs) inhibit axonal growth and regeneration. In the adult nervous system, CSPGs are enriched in perineuronal nets, and their abundance is increased in reactive astrocytes following injury to brain or spinal cord. Degradation of chondroitin sulfate (CS) sugar moieties by the local infusion of the bacterial enzyme chondroitinase ABC (ChaseABC) enhances experience-dependent neuronal plasticity in the adult visual cortex and results in substantially improved behavioral outcomes after spinal cord injury (SCI). Although the positive effects of ChaseABC treatment on neuronal plasticity have been known for some time, the underlying mechanisms remained enigmatic. The receptor protein tyrosine phosphatase sigma (RPTPsigma) has now been identified as a receptor for inhibitory CSPGs. Similarly to ChaseABC treatment, functional ablation of Ptprs, the gene encoding RPTPsigma, promotes neurite outgrowth in the presence of CSPGs in vitro and enhances axonal growth into CSPG-rich scar tissue following SCI in vivo. The discovery of neuronal RPTPsigma as a receptor for inhibitory CSPGs not only provides important mechanistic clues about CSPG function, but also identifies a potential new target for enhancing axonal growth and plasticity after nervous system injury.
Duan
Yuntao
Y
Department of Cell and Developmental Biology and Department of Neurology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Giger
Roman J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009416:Nerve Regeneration / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000201:enzymology*
D011508:Chondroitin Sulfate Proteoglycans; D011956:Receptors, Cell Surface; C487486:chondroitin sulfate proteoglycan receptor, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2