The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI
Abstract
The neurotrophin receptor p75(NTR) is involved in the regulation of axonal elongation by neurotrophins as well as several myelin components, including Nogo, myelin-associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (OMgp). Neurotrophins stimulate neurite outgrowth by inhibiting Rho activity, whereas myelin-derived proteins activate RhoA and thereby inhibit growth. Here we show that direct interaction of the Rho GDP dissociation inhibitor (Rho-GDI) with p75(NTR) initiates the activation of RhoA, and this interaction between p75(NTR) and Rho-GDI is strengthened by MAG or Nogo. We also found that p75(NTR) facilitates the release of prenylated RhoA from Rho-GDI. The peptide ligand that is associated with the fifth alpha helix of p75(NTR) inhibits the interaction between Rho-GDI and p75(NTR), thus silencing the action mediated by p75(NTR). This peptide has potential as a therapeutic agent against the inhibitory cues that block regeneration in the central nervous system.
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The p75NTR-RhoGDI-1 complex formation is strengthened by Nogo and MAG for neurite outgrowth inhibition, while NGF interferes with the binding between p75NTR and RhoGDI-1 to stimulate neurite outgrowth.
“Interestingly, the p75NTR-RhoGDI-1 complex formation has been found strengthened by the myelin-derived protein Nogo and myelin-associated glycoprotein (MAG) for neurite outgrowth inhibition, while the neurotrophin nerve growth factor (NGF) interferes with the binding between p75NTR and RhoGDI-1 that stimulates neurite outgrowth [37].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [37]
p75NTR directly binds RhoGDI-1 and initiates RhoA activation by releasing RhoA from RhoGDI-1.
“For example, the neurotrophin receptor p75NTR directly binds the RhoGDI-1 and initiates RhoA activation by releasing RhoA from RhoGDI-1 [37].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [37]
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- Authors
- Yamashita, T., & Tohyama, M.
- Affiliations
- The University of Osaka (JP)
- Corresponding author
- Yamashita, Toshihide
- ORCID
- Yamashita, Toshihide
- Venue
- Nature Neuroscience
- Published
- 2003-04-14
- Volume
- 6
- Issue
- 5
- Pages
- 461-467
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2019012834
- Cited by
- 460
- References
- 0
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 7 · 2022: 10 · 2021: 16 · 2020: 11 · 2019: 13 · 2018: 14 · 2017: 15 · 2016: 13 · 2015: 20 · 2014: 33 · 2013: 23 · 2012: 26
- FWCI
- 12.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- p75 neurotrophin receptor, RhoA, Rho GDP dissociation inhibitor, RhoA activation, myelin-associated glycoprotein, Nogo, neurite outgrowth, axon elongation, neurotrophins, central nervous system regeneration, peptide ligands
- MeSH terms
- Acute-Phase Proteins, Animals, Cell Line, Ganglia, Spinal, Gene Expression Regulation, Humans, Mice, Inbred C57BL, Neurites, Myelin-Associated Glycoprotein, Guanine Nucleotide Dissociation Inhibitors, Receptor, Nerve Growth Factor, Mice, rho-Specific Guanine Nucleotide Dissociation Inhibitors
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