No Nogo66- and NgR-mediated inhibition of regenerating axons in the zebrafish optic nerve. 2009

Houari Abdesselem, and Aleksandra Shypitsyna, and Gonzalo P Solis, and Vsevolod Bodrikov, and Claudia A O Stuermer
Developmental Neurobiology, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany.

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.

UI MeSH Term Description Entries
D009185 Myelin Proteins MYELIN-specific proteins that play a structural or regulatory role in the genesis and maintenance of the lamellar MYELIN SHEATH structure. Myelin Protein,Protein, Myelin,Proteins, Myelin
D009416 Nerve Regeneration Renewal or physiological repair of damaged nerve tissue. Nerve Tissue Regeneration,Nervous Tissue Regeneration,Neural Tissue Regeneration,Nerve Tissue Regenerations,Nervous Tissue Regenerations,Neural Tissue Regenerations,Regeneration, Nerve,Regeneration, Nerve Tissue,Regeneration, Nervous Tissue,Regeneration, Neural Tissue,Tissue Regeneration, Nerve,Tissue Regeneration, Nervous,Tissue Regeneration, Neural
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009900 Optic Nerve The 2nd cranial nerve which conveys visual information from the RETINA to the brain. The nerve carries the axons of the RETINAL GANGLION CELLS which sort at the OPTIC CHIASM and continue via the OPTIC TRACTS to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the SUPERIOR COLLICULI and the SUPRACHIASMATIC NUCLEI. Though known as the second cranial nerve, it is considered part of the CENTRAL NERVOUS SYSTEM. Cranial Nerve II,Second Cranial Nerve,Nervus Opticus,Cranial Nerve, Second,Cranial Nerves, Second,Nerve, Optic,Nerve, Second Cranial,Nerves, Optic,Nerves, Second Cranial,Optic Nerves,Second Cranial Nerves
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D012160 Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the OPTIC NERVE and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the CHOROID and the inner surface with the VITREOUS BODY. The outer-most layer is pigmented, whereas the inner nine layers are transparent. Ora Serrata
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000070798 Nogo Proteins Myelin proteins that are expressed as three isoforms: Nogo-A, Nogo-B, and Nogo-C. These share a C-terminal reticulon homology domain (RHD), consisting of two hydrophobic membrane domains flanking a 66 amino acid (Nogo-66) hydrophilic region. A long transmembrane region allows conformations that either span the entire membrane or fold into a hairpin conformation. Nogo inhibits NEURITE outgrowth and modulates wiring and the restriction of SYNAPTIC PLASTICITY in the adult central nervous system. It also regulates neurite fasciculation, branching, and extension in the developing nervous system. NI-220 Protein,NI-250 Protein,NI-35 Protein,NI-35-250,Neurite Growth Inhibitor 35-350,Nogo Protein,Nogo-66 Protein,Nogo-A Protein,Nogo-B Protein,Nogo-C Protein,Reticulon 4-B Protein,Reticulon-4 Protein,NI 220 Protein,NI 250 Protein,NI 35 250,NI 35 Protein,Neurite Growth Inhibitor 35 350,Nogo 66 Protein,Nogo A Protein,Nogo B Protein,Nogo C Protein,Reticulon 4 B Protein,Reticulon 4 Protein

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