Martínez-López María José, Alcántara Soledad, Mascaró Cristina, Pérez-Brangulí Francesc, Ruiz-Lozano Pilar, Maes Tamara, Soriano Eduardo, Buesa Carlos
Department of Biochemistry and Molecular Biology, Cell Signaling Group, School of Pharmacy, University of Barcelona, Spain.
Mol Cell Neurosci. 2005 Apr;28(4):599-612. doi: 10.1016/j.mcn.2004.09.016.
The development of the nervous system (NS) requires the coordinated migration of multiple waves of neurons and subsequent processes of neurite maturation, both involving selective guidance mechanisms. In Caenorhabditis elegans, unc-53 codes for a new multidomain protein involved in the directional migration of a subset of cells. We describe here the first functional characterization of the mouse homologue, mouse Neuron navigator 1 (mNAV1), whose expression is largely restricted to the NS during development. EGFP-mNAV1 associates with microtubules (MTs) plus ends present in the growth cone through a new microtubule-binding (MTB) domain. Moreover, its overexpression in transfected cells leads to MT bundling. The abolition of mNAV1 causes loss of directionality in the leading processes of pontine-migrating cells, providing evidence for a role of mNAV1 in mediating Netrin-1-induced directional migration.
神经系统(NS)的发育需要多波神经元的协调迁移以及随后的神经突成熟过程,这两个过程都涉及选择性引导机制。在秀丽隐杆线虫中,unc-53编码一种新的多结构域蛋白,参与一部分细胞的定向迁移。我们在此描述小鼠同源物小鼠神经导航蛋白1(mNAV1)的首次功能特性,其表达在发育过程中主要局限于神经系统。EGFP-mNAV1通过一个新的微管结合(MTB)结构域与生长锥中存在的微管(MT)正端结合。此外,它在转染细胞中的过表达导致微管束形成。mNAV1的缺失导致脑桥迁移细胞前端突起方向性丧失,这为mNAV1在介导Netrin-1诱导的定向迁移中的作用提供了证据。