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NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans.

Nature neuroscience | May 26, 2012

http://www.ncbi.nlm.nih.gov/pubmed/22406547

In the adult mammalian CNS, chondroitin sulfate proteoglycans (CSPGs) and myelin-associated inhibitors (MAIs) stabilize neuronal structure and restrict compensatory sprouting following injury. The Nogo receptor family members NgR1 and NgR2 bind to MAIs and have been implicated in neuronal inhibition. We found that NgR1 and NgR3 bind with high affinity to the glycosaminoglycan moiety of proteoglycans and participate in CSPG inhibition in cultured neurons. Nogo receptor triple mutants (Ngr1(-/-); Ngr2(-/-); Ngr3(-/-); which are also known as Rtn4r, Rtn4rl2 and Rtn4rl1, respectively), but not single mutants, showed enhanced axonal regeneration following retro-orbital optic nerve crush injury. The combined loss of Ngr1 and Ngr3 (Ngr1(-/-); Ngr3(-/-)), but not Ngr1 and Ngr2 (Ngr1(-/-); Ngr2(-/-)), was sufficient to mimic the triple mutant regeneration phenotype. Regeneration in Ngr1(-/-); Ngr3(-/-) mice was further enhanced by simultaneous ablation of Rptpσ (also known as Ptprs), a known CSPG receptor. Collectively, our results identify NgR1 and NgR3 as CSPG receptors, suggest that there is functional redundancy among CSPG receptors, and provide evidence for shared mechanisms of MAI and CSPG inhibition.

Pubmed ID: 22406547 RIS Download

Mesh terms: Analysis of Variance | Animals | Animals, Newborn | Cells, Cultured | Central Nervous System | Chondroitin Sulfate Proteoglycans | Dose-Response Relationship, Drug | Embryo, Mammalian | GPI-Linked Proteins | Ganglia, Spinal | Gene Expression Regulation | Humans | Mice | Mice, Knockout | Mutation | Myelin Proteins | Myelin-Associated Glycoprotein | Nerve Regeneration | Neurons | Optic Nerve Injuries | Protein Binding | Rats | Receptor-Like Protein Tyrosine Phosphatases, Class 4 | Receptors, Cell Surface | Receptors, Tumor Necrosis Factor | Transfection | Tubulin

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Associated grants

  • Agency: NINDS NIH HHS, Id: F31NS061589
  • Agency: NINDS NIH HHS, Id: R01 NS047333
  • Agency: NINDS NIH HHS, Id: R01 NS047333-01A1
  • Agency: NINDS NIH HHS, Id: R01 NS047333-02
  • Agency: NINDS NIH HHS, Id: R01 NS047333-03
  • Agency: NINDS NIH HHS, Id: R01 NS047333-04
  • Agency: NINDS NIH HHS, Id: R01 NS047333-05
  • Agency: NINDS NIH HHS, Id: R01 NS054734
  • Agency: NINDS NIH HHS, Id: R56 NS047333
  • Agency: NINDS NIH HHS, Id: R56 NS047333-06A1
  • Agency: NINDS NIH HHS, Id: R56NS047333
  • Agency: NIGMS NIH HHS, Id: T32 GM007315
  • Agency: NIGMS NIH HHS, Id: T32 GM007315-25
  • Agency: NINDS NIH HHS, Id: T32 NS007489
  • Agency: NINDS NIH HHS, Id: T32 NS007489-08
  • Agency: NINDS NIH HHS, Id: T32 NS007489-08S1
  • Agency: NEI NIH HHS, Id: T32EY017878
  • Agency: NIGMS NIH HHS, Id: T32GM007315

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