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PMID: 15930377 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Nogo-A interacts with the Nogo-66 receptor through multiple sites to create an isoform-selective subnanomolar agonist.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 25 ·No. 22 ·2005-06-01 ·Pages 5298-304

Hu F, Liu BP, Budel S, Liao J, Chin J, Fournier A, Strittmatter SM

Abstract

Nogo is a myelin-derived protein that limits axonal regeneration after CNS injury. A short hydrophilic Nogo-66 loop between two hydrophobic domains of Nogo binds to a Nogo-66 receptor (NgR) to inhibit axonal outgrowth. Inhibition of axon outgrowth and cell spreading by a second Nogo domain, termed Amino-Nogo-A, is thought to be mediated by a distinct receptor complex. Here, we define a novel Nogo-A-specific domain in Amino-Nogo that binds to NgR with nanomolar affinity. This second domain of 24 amino acids does not alter cell spreading or axonal outgrowth. Fusion of the two NgR-binding Nogo-A domains creates a ligand with substantially enhanced affinity for NgR and converts a NgR antagonist peptide to an agonist. Thus, NgR activation by Nogo-A involves multiple sites of interaction between Nogo-A and NgR.

MeSH Terms
Alkaline Phosphatase/genetics Animals Axons/physiology Binding Sites Cell Line Chick Embryo Chlorocebus aethiops GPI-Linked Proteins Glutathione Transferase/genetics Humans In Vitro Techniques Ligands Mice Myelin Proteins/agonists,antagonists & inhibitors,chemistry,genetics,metabolism Nogo Proteins Nogo Receptor 1 Peptides/chemistry,pharmacology Protein Isoforms/agonists,antagonists & inhibitors,metabolism Protein Structure, Tertiary Receptors, Cell Surface/agonists,antagonists & inhibitors,metabolism Recombinant Fusion Proteins/genetics,metabolism
Chemicals
GPI-Linked Proteins Ligands Myelin Proteins Nogo Proteins Nogo Receptor 1 Peptides Protein Isoforms RTN4 protein, human Receptors, Cell Surface Recombinant Fusion Proteins Rtn4 protein, mouse Rtn4r protein, mouse Glutathione Transferase Alkaline Phosphatase
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hu Fenghua
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Liu Betty P
Budel Stephane
Liao Ji
Chin Joanna
Fournier Alyson
Strittmatter Stephen M
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.5235-04.2005
Published
2005-06-01
Pages
5298-304
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC2855126
Subset
IM
Grants
NINDS NIH HHS · R37 NS033020 · United States
NINDS NIH HHS · R01 NS039962-10 · United States
NINDS NIH HHS · R01 NS042304 · United States
NINDS NIH HHS · R01 NS039962 · United States
NINDS NIH HHS · R01 NS042304-08 · United States
NINDS NIH HHS · R37 NS033020-15 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.5235-04.2005 PMC Full Text View journal details
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