Modulation of Receptor Protein Tyrosine Phosphatase Sigma Increases Chondroitin Sulfate Proteoglycan Degradation through Cathepsin B Secretion to Enhance Axon Outgrowth

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Amanda Phuong TranJerry Silver

Abstract

Severed axon tips reform growth cones following spinal cord injury that fail to regenerate, in part, because they become embedded within an inhibitory extracellular matrix. Chondroitin sulfate proteoglycans (CSPGs) are the major axon inhibitory matrix component that is increased within the lesion scar and in perineuronal nets around deafferented neurons. We have recently developed a novel peptide modulator (intracellular sigma peptide) of the cognate receptor of CSPGs, protein tyrosine phosphatase σ (RPTPσ), which has been shown to markedly improve sensorimotor function, micturition, and coordinated locomotor behavior in spinal cord contused rats. However, the mechanism(s) underlying how modulation of RPTPσ mediates axon outgrowth through inhibitory CSPGs remain unclear. Here, we describe how intracellular sigma peptide modulation of RPTPσ induces enhanced protease Cathepsin B activity. Using DRG neurons from female Sprague Dawley rats cultured on an aggrecan/laminin spot assay and a combination of biochemical techniques, we provide evidence suggesting that modulation of RPTPσ regulates secretion of proteases that, in turn, relieves CSPG inhibition through its digestion to allow axon migration though proteoglycan barriers. Unde...Continue Reading

Citations

Aug 15, 2018·Neural Regeneration Research·Philippa Mary WarrenJerry Silver
Aug 15, 2020·Frontiers in Psychiatry·Christine NiemeyerNils C Gassen
Aug 14, 2020·Neural Regeneration Research·Amanda Phuong Tran, Jerry Silver
Jun 20, 2018·International Journal of Molecular Sciences·Kyriakos DalamagkasAlexander M Seifalian
Jun 28, 2019·Frontiers in Cellular Neuroscience·Hiroyuki KatohMichael G Fehlings
Apr 25, 2020·Molecular Neurobiology·Hadi Abou-El-HassanIbrahim Omeis
Apr 13, 2021·Neuroscience Research·Keiji Ibata, Michisuke Yuzaki
Jun 3, 2021·Cell and Tissue Research·Amanda Phuong TranJerry Silver
Jun 3, 2021·International Journal of Molecular Sciences·Kazuma SakamotoKenji Kadomatsu
Jul 6, 2021·Frontiers in Cell and Developmental Biology·Kazuma SakamotoKenji Kadomatsu
Aug 10, 2021·Frontiers in Synaptic Neuroscience·Angelina LesnikovaEero Castrén

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