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NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans.

Nature neuroscience | 2012

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

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Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: T32 NS007489-08S1
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS047333-03
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007315-25
  • Agency: NINDS NIH HHS, United States
    Id: R56 NS047333-06A1
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS047333-05
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS047333
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS047333-04
  • Agency: NINDS NIH HHS, United States
    Id: R56 NS047333
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS047333-02
  • Agency: NIGMS NIH HHS, United States
    Id: T32GM007315
  • Agency: NEI NIH HHS, United States
    Id: T32 EY017878
  • Agency: NINDS NIH HHS, United States
    Id: T32 NS007489-08
  • Agency: NINDS NIH HHS, United States
    Id: T32 NS007489
  • Agency: NINDS NIH HHS, United States
    Id: F31NS061589
  • Agency: NINDS NIH HHS, United States
    Id: F31 NS061589
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS054734
  • Agency: NINDS NIH HHS, United States
    Id: T32 NS076401
  • Agency: RRD VA, United States
    Id: I01 RX000229
  • Agency: NINDS NIH HHS, United States
    Id: R56NS047333
  • Agency: NEI NIH HHS, United States
    Id: T32EY017878
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS047333-01A1
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007315

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