Cellular mechanisms of netrin function: long-range and short-range actions.
Netrins are secreted proteins that direct axon extension and cell migration during neural development. They are bifunctional cues that act as an attractant for some cell types and as a repellent for others. Several lines of evidence suggest that two classes of receptors, the deleted in colorectal cancer (DCC) family and the UNC-5 family, mediate the attractant and repellent response to netrin. Although netrins were first identified as diffusible long-range cues for developing axons, recent findings provide evidence that they also function as short-range cues close to the surface of the cells that produce them. This short-range function of netrin contributes to guiding neurite outgrowth and mediating cell-cell interactions during development and perhaps also in adults.
Kennedy
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Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, QC, Canada. mddy@musica.mcgill.ca
D000818:Animals; D001369:Axons / Q000502:physiology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins; D002465:Cell Movement; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D019143:Evolution, Molecular; D005136:Eye Proteins / Q000502:physiology; D005326:Fetal Proteins / Q000502:physiology; D016163:Genes, DCC; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D005810:Multigene Family; D009124:Muscle Proteins / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D000075386:Netrin Receptors; D000075388:Netrin-1; D000075385:Netrins; D009469:Neuromuscular Junction / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D017978:Receptors, Growth Factor / Q000235:genetics / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000502:physiology; D013045:Species Specificity; D013268:Stimulation, Chemical; D025521:Tumor Suppressor Proteins
D029742:Caenorhabditis elegans Proteins; D005136:Eye Proteins; D005326:Fetal Proteins; D015801:Helminth Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C498815:NTN4 protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D000075385:Netrins; C416214:Ntn4 protein, mouse; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D025521:Tumor Suppressor Proteins; C119569:netrin-3; C077588:UNC-5 protein, C elegans; D000075388:Netrin-1; C088894:netrin-2