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Identification of a new functional domain of Nogo‐A that promotes inflammatory pain and inhibits neurite growth through binding to NgR1
- Source :
- The FASEB Journal. 34:10948-10965
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Nogo-A is a key inhibitory molecule to axon regeneration, and plays diverse roles in other pathological conditions, such as stroke, schizophrenia, and neurodegenerative diseases. Nogo-66 and Nogo-Δ20 fragments are two known functional domains of Nogo-A, which act through the Nogo-66 receptor (NgR1) and sphingosine-1-phosphate receptor 2 (S1PR2), respectively. Here, we reported a new functional domain of Nogo-A, Nogo-A aa 846-861, was identified in the Nogo-A-specific segment that promotes complete Freund's adjuvant (CFA)-induced inflammatory pain. Intrathecal injection of its antagonist peptide 846-861PE or the specific antibody attenuated the CFA-induced inflammatory heat hyperalgesia. The 846-861 PE reduced the content of transient receptor potential vanilloid subfamily member 1 (TRPV1) in dorsal root ganglia (DRG) and decreased the response of DRG neurons to capsaicin. These effects were accompanied by a reduction in LIMK/cofilin phosphorylation and actin polymerization. GST pull-down and fluorescence resonance energy transfer (FRET) assays both showed that Nogo-A aa 846-861 bound to NgR1. Moreover, we demonstrated that Nogo-A aa 846-861 inhibited neurite outgrowth from cortical neurons and DRG explants. We concluded that Nogo-A aa 846-861 is a novel ligand of NgR1, which activates the downstream signaling pathways that inhibit axon growth and promote inflammatory pain.
- Subjects :
- Male
0301 basic medicine
Neurite
Neurogenesis
Nogo Proteins
Neuronal Outgrowth
TRPV1
Pain
TRPV Cation Channels
Biochemistry
Cell Line
Rats, Sprague-Dawley
Mice
03 medical and health sciences
Transient receptor potential channel
0302 clinical medicine
Ganglia, Spinal
Nogo Receptor 1
mental disorders
Neurites
Genetics
medicine
Animals
Humans
Axon
Receptor
Molecular Biology
S1PR2
Inflammation
Neurons
Mice, Inbred ICR
Chemistry
Lim Kinases
Cofilin
Actins
Axons
Nerve Regeneration
Rats
Cell biology
HEK293 Cells
030104 developmental biology
medicine.anatomical_structure
Actin Depolymerizing Factors
Hyperalgesia
Phosphorylation
Female
psychological phenomena and processes
030217 neurology & neurosurgery
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....ddfce82fa2ebc0655dbe6f4a1a28553c