Tam T, Mathews E, Snutch T P, Schafer W R
Department of Biology, University of California at San Diego, La Jolla, California 92093-0349, USA.
Dev Biol. 2000 Oct 1;226(1):104-17. doi: 10.1006/dbio.2000.9854.
Calcium signaling is known to be important for regulating the guidance of migrating neurons, yet the molecular mechanisms underlying this process are not well understood. We have found that two different voltage-gated calcium channels are important for the accurate guidance of postembryonic neuronal migrations in the nematode Caenorhabditis elegans. In mutants carrying loss-of-function alleles of the calcium channel gene unc-2, the touch receptor neuron AVM and the interneuron SDQR often migrated inappropriately, leading to misplacement of their cell bodies. However, the AVM neurons in unc-2 mutant animals extended axons in a wild-type pattern, suggesting that the UNC-2 calcium channel specifically directs migration of the neuronal cell body and is not required for axonal pathfinding. In contrast, mutations in egl-19, which affect a different voltage-gated calcium channel, affected the migration of the AVM and SDQR bodies, as well as the guidance of the AVM axon. Thus, cell migration and axonal pathfinding in the AVM neurons appear to involve distinct calcium channel subtypes. Mutants defective in the unc-43/CaM kinase gene showed a defect in SDQR and AVM positioning that resembled that of unc-2 mutants; thus, CaM kinase may function as an effector of the UNC-2-mediated calcium influx in guiding cell migration.
钙信号传导对于调节迁移神经元的导向作用至关重要，然而这一过程背后的分子机制尚未得到充分理解。我们发现，两种不同的电压门控钙通道对线虫秀丽隐杆线虫胚胎后神经元迁移的精确导向作用至关重要。在携带钙通道基因unc-2功能缺失等位基因的突变体中，触觉受体神经元AVM和中间神经元SDQR常常迁移不当，导致其细胞体位置错误。然而，unc-2突变动物中的AVM神经元以野生型模式延伸轴突，这表明UNC-2钙通道特异性地指导神经元细胞体的迁移，而轴突寻路并不需要它。相比之下，影响另一种电压门控钙通道的egl-19突变会影响AVM和SDQR细胞体的迁移以及AVM轴突的导向。因此，AVM神经元中的细胞迁移和轴突寻路似乎涉及不同的钙通道亚型。unc-43/CaM激酶基因缺陷的突变体在SDQR和AVM定位上表现出与unc-2突变体类似的缺陷；因此，CaM激酶可能作为UNC-2介导的钙内流的效应器来指导细胞迁移。
