Identification of a dithiol-disulfide switch in collapsin response mediator protein 2 (CRMP2) that is toggled in a model of neuronal differentiation

J Biol Chem. 2013 Dec 6;288(49):35117-25. doi: 10.1074/jbc.M113.521443. Epub 2013 Oct 16.


Vertebrate-specific glutaredoxin 2 (Grx2) is expressed in at least two isoforms, mitochondrial Grx2a and cytosolic Grx2c. We have previously shown that cytosolic Grx2 is essential for embryonic development of the brain. In particular, we identified collapsin response mediator protein 2 (CRMP2/DPYSL2), a mediator of the semaphorin-plexin signaling pathway, as redox-regulated target of Grx2c and demonstrated that this regulation is required for normal axonal outgrowth. In this study, we demonstrate the molecular mechanism of this regulation, a specific and reversible intermolecular Cys-504-Cys-504 dithiol-disulfide switch in homotetrameric CRMP2. This switch determines two conformations of the quaternary CRMP2 complex that controls axonal outgrowth and thus neuronal development.

Keywords: CRMP2; Disulfide; Glutaredoxin; Neurodifferentiation; Neuronal Differentiation; Redox Regulation; Redox Signaling; Redox Switch; Thiol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Differentiation
  • Cell Line
  • Cysteine / chemistry
  • Glutaredoxins / genetics
  • Glutaredoxins / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / chemistry*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Models, Neurological*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurogenesis
  • Neurons / cytology*
  • Neurons / metabolism*
  • Oxidation-Reduction
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Protein Structure, Quaternary
  • Protein Subunits
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • GLRX2 protein, human
  • Glutaredoxins
  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Protein Subunits
  • Recombinant Proteins
  • collapsin response mediator protein-2
  • Cysteine