Syntaxin 1 is required for DCC/Netrin-1-dependent chemoattraction of migrating neurons from the lower rhombic lip
Syntaxin 1 is required for DCC/Netrin-1-dependent chemoattraction of migrating neurons from the lower rhombic lip
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DOI：
10.1111/j.1460-9568.2012.08259.x
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发表时间：
2012-11-01
影响因子：
3.4
通讯作者：
Soriano, Eduardo
中科院分区：
文献类型：
--
作者：
Cotrufo, Tiziana;Maria Andres, Rosa;Soriano, Eduardo
定向细胞迁移和轴突导向是神经发育中的重要步骤，具有许多共同的分子机制。发展中的轴突和迁移的神经元的指导可能取决于质膜营业额的精确控制，在选定的区域的前缘和生长锥，分别。先前的结果提供了一种信号传导机制的证据，该机制通过Syntaxin 1（Sytx 1）/TI-VAMP SNARE蛋白将结直肠癌（DCC）/Netrin-1轴突导向和胞吐作用结合在一起。在这里，我们研究了Netrin-1依赖的神经元迁移是否依赖于类似的SNARE机制。我们发现，迁移神经元在下菱形唇（LRL）表达几个陷阱蛋白，DCC与Sytx 1和TI-VAMP在这些细胞中。我们还表明，裂解Sytx 1的肉毒杆菌毒素C1（BoNT/C1）废除Netrin-1依赖的化学吸引迁移神经元，和干扰Sytx 1的功能与shRNA或Sytx 1显性负干扰Netrin-1依赖的化学吸引LRL神经元。这些发现表明，Netrin-1引导迁移神经元需要Sytx 1/DCC相互作用，从而突出了引导信号和调节膜周转的SNARE蛋白之间的关系。
Directed cell migration and axonal guidance are essential steps in neural development that share many molecular mechanisms. The guidance of developing axons and migrating neurons is likely to depend on the precise control of plasmalemma turnover in selected regions of leading edges and growth cones, respectively. Previous results provided evidence of a signaling mechanism that couples chemotropic deleted in colorectal cancer (DCC)/Netrin-1 axonal guidance and exocytosis through Syntaxin1(Sytx1)/TI-VAMP SNARE proteins. Here we studied whether Netrin-1-dependent neuronal migration relies on a similar SNARE mechanism. We show that migrating neurons in the lower rhombic lip (LRL) express several SNARE proteins, and that DCC co-associates with Sytx1 and TI-VAMP in these cells. We also demonstrate that cleavage of Sytx1 by botulinum toxin C1 (BoNT/C1) abolishes Netrin-1-dependent chemoattraction of migrating neurons, and that interference of Sytx1 functions with shRNAs or Sytx1-dominant negatives disrupts Netrin-1-dependent chemoattraction of LRL neurons. These findings indicate that a Sytx1/DCC interaction is required for Netrin-1 guidance of migrating neurons, thereby highlighting a relationship between guidance signaling and SNARE proteins that regulate membrane turnover.