PUBLICATION
No Nogo66- and NgR-mediated inhibition of regenerating axons in the zebrafish optic nerve
- Authors
- Abdesselem, H., Shypitsyna, A., Solis, G.P., Bodrikov, V., and Stuermer, C.A.
- ID
- ZDB-PUB-091221-9
- Date
- 2009
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 29(49): 15489-15498 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Actin Depolymerizing Factors/metabolism
- Animals
- Axons/physiology*
- Glycosylphosphatidylinositols/metabolism
- Growth Cones/physiology
- HeLa Cells
- Hippocampus/physiology
- Humans
- In Vitro Techniques
- Mice
- Myelin Proteins/genetics
- Myelin Proteins/metabolism*
- Nerve Regeneration/physiology*
- Neurites/physiology
- Neurons/physiology
- Optic Nerve/physiology*
- Rats
- Receptors, Cell Surface/metabolism*
- Retina/physiology
- Retinal Ganglion Cells/physiology
- Signal Transduction
- Species Specificity
- Zebrafish
- Zebrafish Proteins/metabolism*
- PubMed
- 20007473 Full text @ J. Neurosci.
Citation
Abdesselem, H., Shypitsyna, A., Solis, G.P., Bodrikov, V., and Stuermer, C.A. (2009) No Nogo66- and NgR-mediated inhibition of regenerating axons in the zebrafish optic nerve. The Journal of neuroscience : the official journal of the Society for Neuroscience. 29(49):15489-15498.
Abstract
In contrast to mammals, lesioned axons in the zebrafish (ZF) optic nerve regenerate and restore vision. This correlates with the absence of the NogoA-specific N-terminal domains from the ZF nogo/rtn-4 (reticulon-4) gene that inhibits regeneration in mammals. However, mammalian nogo/rtn-4 carries a second inhibitory C-terminal domain, Nogo-66, being 70% identical with ZF-Nogo66. The present study examines, (1) whether ZF-Nogo66 is inhibitory and effecting similar signaling pathways upon Nogo66-binding to the Nogo66 receptor NgR and its coreceptors, and (2) whether Rat-Nogo66 on fish, and ZF-Nogo66 on mouse neurons, cause inhibition via NgR. Our results from "outgrowth, collapse and contact assays" suggest, surprisingly, that ZF-Nogo66 is growth-permissive for ZF and mouse neurons, quite in contrast to its Rat-Nogo66 homolog which inhibits growth. The opposite effects of ZF- and Rat-Nogo66 are, in both fish and mouse, transmitted by GPI (glycosylphosphatidylinositol)-anchored receptors, including NgR. The high degree of sequence homology in the predicted binding site is consistent with the ability of ZF- and mammalian-Nogo66 to bind to NgRs of both species. Yet, Rat-Nogo66 elicits phosphorylation of the downstream effector cofilin whereas ZF-Nogo66 has no influence on cofilin phosphorylation--probably because of significantly different Rat- versus ZF-Nogo66 sequences outside of the receptor-binding region effecting, by speculation, recruitment of a different set of coreceptors or microdomain association of NgR. Thus, not only was the NogoA-specific domain lost in fish, but Nogo66, the second inhibitory domain in mammals, and its signaling upon binding to NgR, was modified so that ZF-Nogo/RTN-4 does not impair axon regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping