Zito Arianna, Cartelli Daniele, Cappelletti Graziella, Cariboni Anna, Andrews William, Parnavelas John, Poletti Angelo, Galbiati Mariarita
Dipartimento di Scienze Farmacologiche e Biomolecolari and Centre of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Italia, Via Balzaretti, 9, 20133, Milan, Italy.
Brain Struct Funct. 2014 Jan;219(1):105-18. doi: 10.1007/s00429-012-0487-1. Epub 2012 Dec 5.
Neuritin 1 (Nrn1 or cpg15-1) is an activity-dependent protein involved in synaptic plasticity during brain development, a process that relies upon neuronal migration. By analyzing Nrn1 expression, we found that it is highly expressed in a mouse model of migrating immortalized neurons (GN11 cells), but not in a mouse model of non-migrating neurons (GT1-7 cells). We thus hypothesized that Nrn1 might control neuronal migration. By using complementary assays, as Boyden's microchemotaxis, scratch-wounding and live cell imaging, we found that GN11 cell migration is enhanced when Nrn1 is overexpressed and decreased when Nrn1 is silenced. The effects of Nrn1 in promoting neuronal migration have been then confirmed ex vivo, on rat cortical interneurons, by Boyden chamber assays and focal electroporation of acute embryonic brain slices. Furthermore, we found that Nrn1 level modulation affects GN11 cell morphology. The process is also paralleled by Nrn1-induced α-tubulin post-translational modifications, a well-recognized marker of microtubule stability. Altogether, the data demonstrate a novel function of Nrn1 in promoting migration of neuronal cells and indicate that Nrn1 levels impact on microtubule stability.
神经突蛋白1（Nrn1或cpg15-1）是一种与脑发育过程中突触可塑性相关的活性依赖蛋白，这一过程依赖于神经元迁移。通过分析Nrn1的表达，我们发现它在永生化迁移神经元的小鼠模型（GN11细胞）中高表达，但在非迁移神经元的小鼠模型（GT1-7细胞）中不表达。因此，我们推测Nrn1可能控制神经元迁移。通过使用诸如博伊登微量化学趋化法、划痕损伤和活细胞成像等补充实验，我们发现当Nrn1过表达时GN11细胞迁移增强，而当Nrn1沉默时迁移减弱。随后，通过博伊登室实验和急性胚胎脑片的局部电穿孔，在大鼠皮质中间神经元上进行体外实验，证实了Nrn1在促进神经元迁移方面的作用。此外，我们发现Nrn1水平的调节会影响GN11细胞的形态。这一过程还伴随着Nrn1诱导的α-微管蛋白翻译后修饰，这是微管稳定性的一个公认标志物。总之，这些数据证明了Nrn1在促进神经元细胞迁移方面的新功能，并表明Nrn1水平会影响微管稳定性。
