Nétrine-1 et guidage axonal

Signalisation et traduction asymétrique

Netrin-1 and axonal guidance: indication and asymmetrical translation

Laboratoire Apoptose,Cancer et Développement,Équipe labellisée « La Ligue »,CNRS UMR 5238,Université de Lyon,Centre Léon Bérard,28, rue Laennec,69008 Lyon, France

^* mehlen@lyon.fnclcc.fr

Résumé

Plus de 10 ans après sa découverte, la nétrine-1- première molécule chimioattractive contrôlant le guidage des axones commissuraux - suscite un engouement tout particulier pour son implication dans le développement du système nerveux, mais également pour son rôle dans l’angiogenèse et dans la tumorigenèse via son activité de facteur de survie. Nous traiterons successivement, dans cet article, des voies de la transduction du signal de la nétrine-1 via son récepteur principal DCC (deleted in colorectal cancer) et de la traduction asymétrique de β-actine dans le cône de croissance, en réponse à ce signal nétrine-1/DCC, un mécanisme du processus attraction/répulsion ducône axonal.

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 β-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 β-actin. This process involves both transport of β-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 β-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 β-actin may direct actin polymerization and consequently the migration of the growth cone toward the cue.