NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans
Open accessAbstract
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.
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NgR1 and NgR3 participate in CSPG-mediated neurite outgrowth inhibition, as shown in cultures of cerebellar granule neurons from Ngr single and compound mutants.
“Experiments on cultures of cerebellar granule neurons from Ngr single and compound mutants show that NgR1 and NgR3 participate in CSPG-mediated neurite outgrowth inhibition (Dickendesher et al., 2012).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Dickendesher et al., 2012
NgR1 and NgR3 bind with high specificity to different types of monosulfated and disulfated GAGs.
“NgR1 and NgR3 bind with high specificity to different types of monosulfated and disulfated GAGs.”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Dickendesher et al., 2012
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- Authors
- Dickendesher, T. L., Baldwin, K. T., Mironova, Y. A., Koriyama, Y., Raiker, S. J., Askew, K. L., Wood, A., Geoffroy, C. G., Zheng, B., Liepmann, C. D., Katagiri, Y., Benowitz, L. I., Geller, H. M., & Giger, R. J.
- Affiliations
- University of Michigan (US)
- Boston Children's Hospital (US)
- Pfizer (United States) (US)
- University of California San Diego (US)
- National Institutes of Health (US)
- Corresponding author
- Giger, Roman J
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2012-03-11
- Volume
- 15
- Issue
- 5
- Pages
- 703-712
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3337880
- OpenAlex
- W2157650341
- Cited by
- 449
- References
- 50
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 20 · 2023: 26 · 2022: 21 · 2021: 27 · 2020: 39 · 2019: 21 · 2018: 40 · 2017: 38 · 2016: 27 · 2015: 47 · 2014: 55 · 2013: 42 · 2012: 15
- FWCI
- 20.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- U.S. Department of Veterans Affairs (I01 RX000229)
- Japan Society for the Promotion of Science (22791651)
- National Eye Institute (T32EY017878)
- National Institute of General Medical Sciences (T32GM007315)
- National Institute of Neurological Disorders and Stroke (R01NS054734, R01NS047333, R56NS047333, F31NS061589, T32NS007489, T32NS076401)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- NgR1, Nogo receptor, chondroitin sulfate proteoglycans, myelin-associated inhibitors, axon growth inhibition, axon regeneration, optic nerve crush, glycosaminoglycan binding, functional redundancy, central nervous system injury
- MeSH terms
- Nogo Receptor 1, Analysis of Variance, Animals, Animals, Newborn, Cells, Cultured, Central Nervous System, Dose-Response Relationship, Drug, Embryo, Mammalian, Ganglia, Spinal, Gene Expression Regulation, Humans, Mutation, Myelin Proteins, Nerve Regeneration, Neurons, Protein Binding, Chondroitin Sulfate Proteoglycans, Receptors, Cell Surface, Transfection, Tubulin, Receptors, Tumor Necrosis Factor, Mice, Knockout, Myelin-Associated Glycoprotein, Optic Nerve Injuries, Mice, Rats, Receptor-Like Protein Tyrosine Phosphatases, Class 4, GPI-Linked Proteins
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