RGD Reference Report - AMIGO3 is an NgR1/p75 co-receptor signalling axon growth inhibition in the acute phase of adult central nervous system injury. - Rat Genome Database

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AMIGO3 is an NgR1/p75 co-receptor signalling axon growth inhibition in the acute phase of adult central nervous system injury.

Authors: Ahmed, Zubair  Douglas, Michael R  John, Gabrielle  Berry, Martin  Logan, Ann 
Citation: Ahmed Z, etal., PLoS One. 2013 Apr 16;8(4):e61878. doi: 10.1371/journal.pone.0061878. Print 2013.
RGD ID: 14390159
Pubmed: (View Article at PubMed) PMID:23613963
DOI: Full-text: DOI:10.1371/journal.pone.0061878

Axon regeneration in the injured adult CNS is reportedly inhibited by myelin-derived inhibitory molecules, after binding to a receptor complex comprised of the Nogo-66 receptor (NgR1) and two transmembrane co-receptors p75/TROY and LINGO-1. However, the post-injury expression pattern for LINGO-1 is inconsistent with its proposed function. We demonstrated that AMIGO3 levels were significantly higher acutely than those of LINGO-1 in dorsal column lesions and reduced in models of dorsal root ganglion neuron (DRGN) axon regeneration. Similarly, AMIGO3 levels were raised in the retina immediately after optic nerve crush, whilst levels were suppressed in regenerating optic nerves, induced by intravitreal peripheral nerve implantation. AMIGO3 interacted functionally with NgR1-p75/TROY in non-neuronal cells and in brain lysates, mediating RhoA activation in response to CNS myelin. Knockdown of AMIGO3 in myelin-inhibited adult primary DRG and retinal cultures promoted disinhibited neurite growth when cells were stimulated with appropriate neurotrophic factors. These findings demonstrate that AMIGO3 substitutes for LINGO-1 in the NgR1-p75/TROY inhibitory signalling complex and suggests that the NgR1-p75/TROY-AMIGO3 receptor complex mediates myelin-induced inhibition of axon growth acutely in the CNS. Thus, antagonizing AMIGO3 rather than LINGO-1 immediately after CNS injury is likely to be a more effective therapeutic strategy for promoting CNS axon regeneration when combined with neurotrophic factor administration.

Annotation

Disease Annotations    

Gene Ontology Annotations    

Biological Process

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Amigo3  (adhesion molecule with Ig like domain 3)
Ngfr  (nerve growth factor receptor)
Rtn4r  (reticulon 4 receptor)

Genes (Mus musculus)
Amigo3  (adhesion molecule with Ig like domain 3)

Genes (Homo sapiens)
AMIGO3  (adhesion molecule with Ig like domain 3)


Additional Information