Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia; Competence Centre for Cancer Research, Tallinn, Estonia.
Competence Centre for Cancer Research, Tallinn, Estonia.
Exp Cell Res. 2014 Aug 1;326(1):174-84. doi: 10.1016/j.yexcr.2014.06.005. Epub 2014 Jun 19.
Semaphorins and their receptors plexins are implicated in various processes in the nervous system, but how B-plexins regulate the growth of dendrites remains poorly characterized. We had previously observed that Plexin-B1 and B3 interact with microtubule end-binding proteins (EBs) that are central adapters at growing microtubule tips, and this interaction is involved in neurite growth. Therefore, we hypothesized that plexins regulate microtubule dynamics and through that also dendritogenesis. The role of all three B-plexins was systematically examined in these processes. B-plexins and their ligand Semaphorin-4D influence the dynamics of microtubule tips both EB-dependently and independendently. EB3 as well as Plexin-B1, B2 and B3 turned out to have a significant role in the development of dendritic arbor of rat hippocampal neurons. Our results clearly indicate that semaphorin-plexin-EB pathway is one molecular mechanism how extracellular guidance cues are translated into intracellular mechanics. Taken together, Semaphorin-4D and B-plexins modulate the dynamic behavior of microtubule tips, and are therefore important in neurite growth.
信号蛋白及其受体神经纤毛蛋白参与神经系统的各种过程,但 B 类神经纤毛蛋白如何调节树突的生长仍知之甚少。我们之前观察到 Plexin-B1 和 B3 与微管末端结合蛋白 (EBs) 相互作用,EBs 是生长中的微管末端的核心衔接物,这种相互作用参与了神经突的生长。因此,我们假设神经纤毛蛋白调节微管动力学,并通过这种方式调节树突发生。我们系统地研究了这三种 B 类神经纤毛蛋白在这些过程中的作用。B 类神经纤毛蛋白及其配体 Semaforin-4D 影响微管末端的动力学,既依赖于 EB,也独立于 EB。EB3 以及 Plexin-B1、B2 和 B3 显然在大鼠海马神经元树突分支的发育中起着重要作用。我们的结果清楚地表明,信号蛋白-神经纤毛蛋白-EB 途径是一种将细胞外导向信号转化为细胞内力学的分子机制。总之,Semaforin-4D 和 B 类神经纤毛蛋白调节微管末端的动态行为,因此在神经突生长中很重要。