Jarjour Andrew A, Bull Sarah-Jane, Almasieh Mohammadali, Rajasekharan Sathyanath, Baker K Adam, Mui Jeannie, Antel Jack P, Di Polo Adriana, Kennedy Timothy E
Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A2B4.
J Neurosci. 2008 Oct 22;28(43):11003-14. doi: 10.1523/JNEUROSCI.3285-08.2008.
Paranodal axoglial junctions are essential for the segregation of myelinated axons into distinct domains and efficient conduction of action potentials. Here, we show that netrin-1 and deleted in colorectal cancer (DCC) are enriched at the paranode in CNS myelin. We then address whether netrin-1 signaling influences paranodal adhesion between oligodendrocytes and axons. In the absence of netrin-1 or DCC function, oligodendroglial paranodes initially develop and mature normally but later become disorganized. Lack of DCC or netrin-1 resulted in detachment of paranodal loops from the axonal surface and the disappearance of transverse bands. Furthermore, the domain organization of myelin is compromised in the absence of netrin-1 signaling: K+ channels inappropriately invade the paranodal region, and the normally restricted paranodal distribution of Caspr expands longitudinally along the axon. Our findings identify an essential role for netrin-1 and DCC regulating the maintenance of axoglial junctions.
结旁轴突-胶质细胞连接对于有髓轴突分隔成不同区域以及动作电位的高效传导至关重要。在此，我们表明，在中枢神经系统髓鞘的结旁区域，网蛋白-1和结直肠癌缺失基因（DCC）含量丰富。然后，我们探讨网蛋白-1信号是否影响少突胶质细胞与轴突之间的结旁黏附。在缺乏网蛋白-1或DCC功能的情况下，少突胶质细胞结旁结构最初正常发育和成熟，但随后变得紊乱。缺乏DCC或网蛋白-1导致结旁环从轴突表面脱离，横向带消失。此外，在缺乏网蛋白-1信号的情况下，髓鞘的区域组织受到损害：钾离子通道不恰当地侵入结旁区域，并且通常局限于结旁的Caspr分布沿轴突纵向扩展。我们的研究结果确定了网蛋白-1和DCC在调节轴突-胶质细胞连接维持方面的重要作用。
