Regulation of nerve growth and patterning by cell surface protein disulphide isomerase
Regulation of nerve growth and patterning by cell surface protein disulphide isomerase
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DOI：
10.7554/elife.54612
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发表时间：
2020-05-28
期刊：
影响因子：
7.7
通讯作者：
Keynes, Roger J.
中科院分区：
文献类型：
--
作者：
Cook, Geoffrey M. W.;Sousa, Catia;Keynes, Roger J.
生长轴突的接触排斥是脊神经形成的重要机制。在鸟类和哺乳动物中，胚胎体节产生一系列线性的不可穿透的屏障，迫使轴突生长锥在向身体目标延伸时穿过每个体节的一半。这项研究表明，蛋白质二硫键异构酶提供了这些障碍的关键组成部分，介导鸡半体节细胞表面的接触排斥。通过一系列抑制酶活性的方法，在体内和体外均降低排斥。该活性在启动调节生长锥细胞骨架的一氧化氮/S-亚硝基化依赖性信号转导途径中至关重要。大鼠前脑灰质提取物含有类似的活性，并且该酶在培养的人星形胶质细胞和大鼠皮质星形胶质细胞的表面表达。我们认为这个系统是增选在大脑中，以抵消和调节异常的神经末梢生长。
Contact repulsion of growing axons is an essential mechanism for spinal nerve patterning. In birds and mammals the embryonic somites generate a linear series of impenetrable barriers, forcing axon growth cones to traverse one half of each somite as they extend towards their body targets. This study shows that protein disulphide isomerase provides a key component of these barriers, mediating contact repulsion at the cell surface in chick half-somites. Repulsion is reduced both in vivo and in vitro by a range of methods that inhibit enzyme activity. The activity is critical in initiating a nitric oxide/S-nitrosylation-dependent signal transduction pathway that regulates the growth cone cytoskeleton. Rat forebrain grey matter extracts contain a similar activity, and the enzyme is expressed at the surface of cultured human astrocytic cells and rat cortical astrocytes. We suggest this system is co-opted in the brain to counteract and regulate aberrant nerve terminal growth.