A regulated switch of chick neurofascin isoforms modulates ligand recognition and neurite extension.
Neural cell adhesion molecule neurofascin regulates the induction of neurite outgrowth, the establishment of synaptic connectivity and myelination. Neurofascin isoforms are generated by spatially and temporally controlled alternative splicing. Isoform NF166 is predominantly expressed in dorsal root ganglia from embryonal day 5 (E5) to E8, and a further neurofascin isoform NF185 appears at E9. Expression of neurofascin and its binding partner axonin-1 on sensory fibers implies functional interactions for neurite outgrowth. E7 sensory neurons require NF166-axonin-1 interactions for neurite extension, accordingly. The contribution of NF166-axonin-1 interaction for neurite outgrowth decreases in parallel with the appearance of NF185 on sensory neurons at E9. This finding may be explained by (1) alleviated intrinsic capability to use axonin-1 as a cellular receptor and (2) reduced binding of axonin-1 to NF185. Finally, NF166, but not NF185, serves as a cellular receptor for neurite induction via homophilic interactions with a neurofascin substrate.
Pruss
Thomas
T
NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen, NMI, Markwiesenstr. 55, 72770 Reutlingen, Germany.
Kranz
Eva Ursula
EU
Niere
Marc
M
Volkmer
Hansjürgen
H
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D002642:Chick Embryo; D058969:Contactin 2; D005091:Exons; D005727:Ganglia, Spinal / Q000166:cytology; D008024:Ligands; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism* / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D058969:Contactin 2; D008024:Ligands; D009414:Nerve Growth Factors; C504595:Nfasc protein, Gallus gallus; D020033:Protein Isoforms