Modulation of proteoglycan receptor regulates RhoA/CRMP2 pathways and promotes axonal myelination

Neurosci Lett. 2021 Aug 24:760:136079. doi: 10.1016/j.neulet.2021.136079. Epub 2021 Jun 21.


The function of the myelinating system is important because a defective myelin sheath results in various nervous disorders, including multiple sclerosis and peripheral neuropathies. The dorsal root entry zone (DREZ) is a transitional area between the central nervous system (CNS) and the peripheral nervous system (PNS) that is generated by two types of cells-oligodendrocytes and Schwann cells (SCs). It is well known that after injury the extracellular matrix, including the CSPG, impairs axonal myelination by activating protein tyrosine phosphatase-σ (PTPσ) in both cells. The Intracellular Sigma Peptide (ISP) is memetic of the PTPσ wedge region. It competitively binds to PTPσ and regulates the downstream signaling of RhoA. In the present study, we aimed to investigate whether the ISP increased myelination in vivo and in vitro. The in vitro assay was meant to further verify the in vivo mechanisms. We observed that ISP administration could increase axonal myelination both in vivo and in vitro. Furthermore, we provide evidence that, in oligodendrocytes and Schwann cells, the myelination-induced effects of ISP application entail an inverse expression of the RhoA/CRMP2 signaling pathway. Overall, our results indicate that the ISP modulation of PTPσ enhances axonal myelination via the RhoA/CRMP2 signaling pathways.

Keywords: ISP; Myelination; OPCs; PTPσ; SCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Disease Models, Animal
  • Female
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / injuries*
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Myelin Sheath / drug effects*
  • Myelin Sheath / metabolism
  • Nerve Regeneration / drug effects*
  • Nerve Tissue Proteins / metabolism
  • Oligodendroglia / cytology
  • Oligodendroglia / drug effects
  • Oligodendroglia / metabolism
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • Proteoglycans / metabolism
  • Rats
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism*
  • Schwann Cells / cytology
  • Schwann Cells / drug effects
  • Schwann Cells / metabolism
  • Signal Transduction / drug effects
  • rho GTP-Binding Proteins / metabolism


  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Peptides
  • Proteoglycans
  • collapsin response mediator protein-2
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
  • RhoA protein, rat
  • rho GTP-Binding Proteins