The Antioxidant Enzyme Prdx1 Controls Neuronal Differentiation by Thiol-Redox-Dependent Activation of GDE2
Open accessAbstract
The six-transmembrane protein GDE2 controls the onset and progression of spinal motor neuron differentiation through extracellular glycerophosphodiester phosphodiesterase metabolism. Although this process is likely to be tightly regulated, the relevant mechanisms that modulate its activity are unknown. Here we show that the antioxidant scavenger peroxiredoxin1 (Prdx1) interacts with GDE2, and that loss of Prdx1 causes motor neuron deficits analogous to GDE2 ablation. Prdx1 cooperates with GDE2 to drive motor neuron differentiation, and this synergy requires Prdx1 thiol-dependent catalysis. Prdx1 activates GDE2 through reduction of an intramolecular disulfide bond that bridges its intracellular N- and C-terminal domains. GDE2 variants incapable of disulfide bond formation acquire independence from Prdx1 and are potent inducers of motor neuron differentiation. These findings define Prdx1 as a pivotal regulator of GDE2 activity and suggest roles for coupled thiol-redox-dependent cascades in controlling neuronal differentiation in the spinal cord.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
GDE2-PRDX1 thiol reduction stimulates GDE2 activity at the cell surface.
“GDE2-PRDX1 thiol reduction stimulates GDE2 activity at the cell surface (45).”
From GDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein (2021) · cites this paper as [45]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Neuronal specification in the spinal cord: inductive signals and transcriptional codes
Jessell, T. M. (2000) · Nature Reviews Genetics · doi:10.1038/35049541 · Cited by 2,089 · see citing works
Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II
Choi, M. H., Lee, I. K., Kim, G. W., Kim, B. U., Han, Y.-H., Yu, D.-Y., Park, H. S., Kim, K. Y., Lee, J. S., Choi, C., et al. (2005) · Nature · doi:10.1038/nature03587 · Cited by 403 · see citing works
Flagged first, then by citations
Research works printed but not linked: 35
- Arnér ES Holmgren A 2006 The thioredoxin system in cancer Semin Cancer Biol 16 420 426 17092741
- Bertram JS 2000 The molecular biology of cancer Mol Aspects Med 21 167 223 11173079
- Burgoyne JR Madhani M Cuello F Charles RL Brennan JP Schröder E Browning DD Eaton P 2007 Cysteine Redox Sensor in PKGIa Enables Oxidant-Induced Activation Science 317 1393 1397 17717153
- Chenn A Walsh CA 2002 Regulation of cerebral cortical size by control of cell cycle exit in neural precursors Science 297 365 369 12130776
- Delaunay A Pflieger D Barrault MB Vinh J Toledano MB 2002 A thiol peroxidase is an H202 receptor and redox-transducer in gene activation Cell 111 471 481 12437921
- Egler RA Fernandes E Rothermund K Sereika S de Souza-Pinto N Jaruga P Dizdaroglu M Prochownik EV 2005 Regulation of reactive oxygen species, DNA damage, and c-Myc function by peroxiredoxin 1 Oncogene 24 8038 8050 16170382
- Flohe L Budde H Bruns K Castro H Clos J Hofmann B Kansal-Kalavar S Krumme D Menge U Plank-Schumacher K 2002 Tryparedoxin peroxidase of Leishmania donovani: Molecular cloning, heterologous expression, specificity and catalytic mechanism Arch Biochem and Biophys 397 324 335 11795890
- Funato Y Michiue T Asashima M Miki H 2006 The thioredoxin-related redox-regulating protein nucleoredoxin inhibits Wnt-β-catenin signaling through Dishevelled Nature Cell Bio 8 501 508 16604061
- Helms AW Johnson JE 2003 Specification of dorsal spinal cord interneurons Curr Opin Neurobiol 13 42 49 12593981
- Hollyday M 2001 Neurogenesis in the vertebrate neural tube Int J Dev Neurosci 19 161 173 11255030
- Jang HH Lee KO Chi YH Jung BG Park SK Park JH Lee JR Lee SS Moon JC Jeong WY 2004 Two enzymes in one: two yeast peroxiredoxins display oxidative stress-dependent switching from a peroxidase to a molecular chaperone function Cell 117 625 635 15163410
- Kintner C 2002 Neurogenesis in embryos and in adult neural stem cells J Neurosci 22 639 643 11826093 PMC6758480
- Lee SK Lee B Ruiz EC Pfaff SL 2005 Olig2 and Ngn2 function in opposition to modulate gene expression in motor neuron progenitor cells Genes and Dev 19 282 294 15655114 PMC545894
- Leichert LI Jakob U 2004 Protein thiol modifications visualized in vivo PLoS Biology 1723 1737 PMC521172 15502869
- Megason SG McMahon AP 2002 A mitogen gradient of dorsal midline Wnts organizes growth in the CNS Development 129 2087 2098 11959819
- Mizuguchi R Sugimori M Takebayashi H Kosako H Nagao M Yoshida S Nabeshima Y Shimamura K Nakafuku M 2001 Combinatorial roles of olig2 and neurogenin2 in the coordinated induction of pan-neuronal and subtype-specific properties of motoneurons Neuron 31 757 771 11567615
- Montemartini M Kalisz HM Hecht HJ Steinert P Flohe L 1999 Activation of site cysteine residues in the peroxiredoxin-type tryparedoxin peroxidase of Crithidia fasciculate Eur J Biochem 264 516 524 10491099
- Neumann CA Krause DS Carman CV Das S Dubey DP Abraham JL Bronson RT Fujiwara Y Orkin SH Van Etten RA 2003 Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumor suppression Nature 242 561 565 12891360
- Nogusa Y Fujioka Y Komatsu R Kato N Yanaka N 2004 Isolation and characterization of two serpentine membrane proteins containing glycerophosphodiester phosphodiesterase, GDE2 and GDE6 Gene 337 173 179 15276213
- Novitch BG Chen AI Jessell TM 2001 Coordinate regulation of motor neuron subtype identity and pan-neuronal properties by the bHLH repressor Olig2 Neuron 31 773 789 11567616
- Novitch BG Wichterle H Jessell TM Sockanathan S 2003 A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification Neuron 40 81 95 14527435
- Paget MS Buttner MJ 2003 Thiol-based regulatory switches Annu Rev Genet 37 91 121 14616057
- Rao M Baraban J Rajaii F Sockanathan S 2004 In vivo comparative study of RNAi methodologies by in ovo electroporation in the chick embryo Dev Dyn 231 592 600 15376322
- Rao M Sockanathan S 2005 Transmembrane protein GDE2 induces motor neuron differentiation in vivo Science 309 2212 2215 16195461
- Rhee SG Chae HZ Kim K 2005 Peroxiredoxins: A historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling Free Rad Bio and Medicine 38 1543 1552 15917183
- Ritz D Lim J Reynolds CM Poole LB Beckwith J 2001 Conversion of a peroxiredoxin into a disulfide reductase by a triplet repeat expansion Science 294 158 160 11588261
- Santelli E Schwarzenbacher R McMullan D Biorac T Brinen LS Canaves JM Cambell J Dai X Deacon AM Elsliger MA 2004 Crystal structure of a glycerophosphodiester phosphodiesterase (GDPD) from Thermotoga maritima (TM1621) at 1.60 A resolution Proteins 56 167 170 15162496
- Sevier CS Qu H Heldman N Gross E Fass D Kaiser CA 2007 Modulation of cellular disulfide-bond formation and the ER redox environment by feedback regulation of Ero1 Cell 129 333 344 17448992
- Sevier CS Kaiser CA 2002 Formation and transfer of disulphide bonds in living cells Nat rev Mol Cell Bio 3 836 847 12415301
- Wood ZA Schroder E Harris JR Poole LB 2003 Structure, mechanism and regulation of peroxiredoxins Trends in Biochem Sci 28 32 40 12517450
- Yanaka N Imai Y Kawai E Akatsuka H Wakimoto K Nogusa Y Kato N Chiba H Kotani E Omori K 2003 Novel membrane protein containing glycerophosphodiester phosphodiesterase motif is transiently expressed during osteoblast differentiation J Biol Chem 44 43595 43602 12933806
- Yanaka N Nogusa Y Fujioka Y Yamashita Y Kato N 2007 Involvement of membrane protein GDE2 in retinoic acid-induced neurite formation in Neuro2A cells FEBS Lett 581 712 718 17275818
- Yanaka N 2007 Mammalian glycerophosphodiester phosphodiesterases Biosci Biotechnol Biochem 71 1811 1818 17690467
- Zechner D Fujita Y Hülsken J Müller T Walther I Taketo MM Crenshaw EB 3rd Birchmeier W Birchmeier C 2003 beta-Catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system Dev Biol 258 406 418 12798297
- Zheng B Berrie CP Corda D Farquhar MG 2003 GDE1/MIR16 is a glycerophosphoinositol phosphodiesterase regulated by stimulation of G-protein coupled receptors Proc Nat Acad Sci (USA) 100 1745 1750 12576545 PMC149904
Cited by
Sorted by citations
Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides
Rhee, S. G., Woo, H. A., Kil, I. S., & Bae, S. H. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.283432 · Cited by 603 · see citing works
Rhee, S. G., & Woo, H. A. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3393 · Cited by 463 · see citing works
GDE2 Regulates Subtype-Specific Motor Neuron Generation through Inhibition of Notch Signaling
Sabharwal, P., Lee, C., Park, S., Rao, M., & Sockanathan, S. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.028 · Cited by 54 · see citing works
Self-citationGDE2-RECK controls ADAM10 α-secretase–mediated cleavage of amyloid precursor protein
Nakamura, M., Li, Y., Choi, B.-R., Matas-Rico, E., Troncoso, J., Takahashi, C., & Sockanathan, S. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe6178 · Cited by 38 · see citing works
Self-citationPrutton, K. M., Marentette, J. O., Leifheit, B. A., Esquer, H., LaBarbera, D. V., Anderson, C. C., Maclean, K. N., & Roede, J. R. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.04.015 · Cited by 13 · see citing works
- Authors
- Yan, Y., Sabharwal, P., Rao, M., & Sockanathan, S.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Sockanathan, Shanthini
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 138
- Issue
- 6
- Pages
- 1209-1221
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2748999
- OpenAlex
- W2096870699
- Cited by
- 103
- References
- 2
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 13 · 2020: 6 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 12 · 2014: 4 · 2013: 8 · 2012: 10
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R56NS046336, R01NS046336)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- peroxiredoxin 1, glycerophosphodiester phosphodiesterase, motor neuron differentiation, disulfide bond reduction, protein-protein interaction, spinal cord, antioxidant enzymes
- MeSH terms
- Animals, Cell Differentiation, Chick Embryo, Motor Neurons, Oxidation-Reduction, Phosphoric Diester Hydrolases, Spine, Sulfhydryl Compounds, Avian Proteins, Mice, Peroxiredoxins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
