title: [Netrin-1 and axonal guidance: signaling and asymmetrical translation].
abstract: More than 10 years after its initial discovery, netrin-1 - the first described chimioattractive molecule controlling the guidance of the commissural axons - has recently known a unsuspected wave of interest because of its implication in the development of the nervous system but also, more recently, fot its role in angiogenesis and tumorigenesis. Because, of a series of recent publications on netrin-1 signaling, we propose here to describe the recent insight in netrin-1 signaling via its main receptor DCC (deleted in colorectal cancer), and the recent discovery that netrin controls the assymetric distribution of beta-actin in the growth cone. Thus, it seems that netrin-1, but also the neurotrophic factor BDNF, controls acute growth cone responses such as collapse and turning by the regulation of localized protein translation, such as beta-actin. This process involves both transport of beta-actin mRNA, bound to Vg1RBP, to specific locations, and mRNA translation upon stimulation by local activation of the translation initiation regulator eIF-4E-binding protein 1. Indeed, Netrin-1 induces the movement of Vg1RBP granules into filopodia, and triggers a polarized increase in beta-actin translation on the near side of the growth cone before growth cone turning. The binding of BDNF to its receptor Trk has a similar effect for growth cone attraction, althought it is differentially regulated. Thus, this asymetrically synthesized beta-actin may direct actin polymerization and consequently the migration of the growth cone toward the cue.
authors.affiliation: Laboratoire Apoptose, Cancer et Développement, Equipe labellisée La Ligue, CNRS UMR 5238, Université de Lyon, Centre Léon Bérard, 28, rue Laennec, 69008 Lyon, France. mehlen@lyon.fnclcc.fr
authors.forename: Patrick
authors.initials: P
authors.lastname: Mehlen
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rama
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D016764:Cell Polarity; D002633:Chemotaxis / Q000502:physiology; D003110:Colonic Neoplasms / Q000235:genetics; D000075389:DCC Receptor; D016163:Genes, DCC; D020439:Growth Cones / Q000502:physiology; D006801:Humans; D009024:Morphogenesis / Q000502:physiology; D009414:Nerve Growth Factors / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D000075386:Netrin Receptors; D000075388:Netrin-1; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D000199:Actins; D019208:Brain-Derived Neurotrophic Factor; D000075389:DCC Receptor; C501909:DCC protein, human; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D011494:Protein Kinases