No Nogo66- and NgR-mediated inhibition of regenerating axons in the zebrafish optic nerve

Houari Abdesselem, Aleksandra Shypitsyna, Gonzalo P. Solis, Vsevolod Bodrikov, Claudia A.O. Stuermer

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)15489-15498
Number of pages10
JournalJournal of Neuroscience
Volume29
Issue number49
DOIs
Publication statusPublished - 9 Dec 2009
Externally publishedYes

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Zebrafish
Optic Nerve
Axons
Actin Depolymerizing Factors
Mammals
Fishes
Inhibition (Psychology)
Regeneration
Phosphorylation
Neurons
Glycosylphosphatidylinositols
Aptitude
Growth
Sequence Homology
Binding Sites

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

No Nogo66- and NgR-mediated inhibition of regenerating axons in the zebrafish optic nerve. / Abdesselem, Houari; Shypitsyna, Aleksandra; Solis, Gonzalo P.; Bodrikov, Vsevolod; Stuermer, Claudia A.O.

In: Journal of Neuroscience, Vol. 29, No. 49, 09.12.2009, p. 15489-15498.

Research output: Contribution to journalArticle

Abdesselem, Houari ; Shypitsyna, Aleksandra ; Solis, Gonzalo P. ; Bodrikov, Vsevolod ; Stuermer, Claudia A.O. / No Nogo66- and NgR-mediated inhibition of regenerating axons in the zebrafish optic nerve. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 49. pp. 15489-15498.
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