title: Identification of a dithiol-disulfide switch in collapsin response mediator protein 2 (CRMP2) that is toggled in a model of neuronal differentiation.
abstract: 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.
authors.affiliation: From the Institute for Medical Biochemistry and Molecular Biology, University Medicine, Ernst-Moritz-Arndt-University Greifswald, 17475 Greifswald, Germany and.
authors.forename: Manuela
authors.initials: M
authors.lastname: Gellert
authors.forename: Simone
authors.initials: S
authors.lastname: Venz
authors.forename: Jessica
authors.initials: J
authors.lastname: Mitlöhner
authors.forename: Catherine
authors.initials: C
authors.lastname: Cott
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Hanschmann
authors.forename: Christopher Horst
authors.initials: CH
authors.lastname: Lillig
mesh_terms: D000595:Amino Acid Sequence; D002454:Cell Differentiation; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry; D054477:Glutaredoxins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010084:Oxidation-Reduction; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: C516008:GLRX2 protein, human; D054477:Glutaredoxins; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D011994:Recombinant Proteins; C095114:collapsin response mediator protein-2; D003545:Cysteine
keywords: CRMP2; Disulfide; Glutaredoxin; Neurodifferentiation; Neuronal Differentiation; Redox Regulation; Redox Signaling; Redox Switch; Thiol