Manitt Colleen, Kennedy Timothy E
Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, QC H3A 2B4, Canada.
Prog Brain Res. 2002;137:425-42. doi: 10.1016/s0079-6123(02)37034-1.
Netrins are a family of secreted proteins that direct the migration of cells and axonal growth cones during neural development. They are bifunctional cues, attracting some cell types and repelling others. Netrins function as either short- or long-range cues, in some circumstances acting close to the surface of the cells that produce them and in other cases at a distance. Two classes of receptors mediate the response to netrin-1, the deleted in colorectal cancer family and the UNC-5 homolog family. Although netrin function has been extensively studied in the embryonic nervous system, netrin-1 is expressed in the adult mammalian spinal cord at a level similar to that in the embryonic CNS. In the adult and embryonic CNS, the majority of netrin-1 protein is not freely soluble but is associated with membranes and extracellular matrix. This distribution is consistent with netrin-1 acting as a short-range cue. Here we present a model whereby netrin-1 in the embryonic neural epithelium could act as a membrane-associated long-range cue. Netrin-1 is expressed in the adult by multiple types of neurons and by myelinating glia: oligodendrocytes in the CNS and Schwann cells in the PNS. In the white matter of the adult CNS, netrin-1 protein is absent from compact myelin but enriched in periaxonal myelin at the interface between axons and oligodendrocytes. This distribution suggests that in the adult nervous system netrin-1 may function to mediate cell-cell interactions. Furthermore, netrin receptor expression persists in neurons following injury, raising the possibility that netrin-1 may influence axonal regeneration.
网蛋白是一类分泌蛋白家族，在神经发育过程中指导细胞迁移和轴突生长锥的生长。它们是双功能信号，对某些细胞类型起吸引作用，对其他细胞类型起排斥作用。网蛋白可作为短程或长程信号，在某些情况下作用于产生它们的细胞表面附近，而在其他情况下则作用于远处。两类受体介导对网蛋白-1的反应，即结直肠癌缺失家族和UNC-5同源家族。尽管网蛋白的功能已在胚胎神经系统中得到广泛研究，但网蛋白-1在成年哺乳动物脊髓中的表达水平与胚胎中枢神经系统中的水平相似。在成年和胚胎中枢神经系统中，大多数网蛋白-1蛋白不是自由可溶的，而是与膜和细胞外基质相关联。这种分布与网蛋白-1作为短程信号的作用一致。在此，我们提出一个模型，即胚胎神经上皮中的网蛋白-1可以作为一种膜相关的长程信号。成年期网蛋白-1由多种类型的神经元以及形成髓鞘的神经胶质细胞表达：中枢神经系统中的少突胶质细胞和周围神经系统中的施万细胞。在成年中枢神经系统的白质中，紧密髓鞘中不存在网蛋白-1蛋白，但在轴突与少突胶质细胞之间的界面处的轴周髓鞘中富集。这种分布表明，在成年神经系统中，网蛋白-1可能起到介导细胞间相互作用的作用。此外，损伤后神经元中网蛋白受体的表达持续存在，这增加了网蛋白-1可能影响轴突再生的可能性。
