Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Eur J Neurosci. 2013 May;37(9):1404-12. doi: 10.1111/ejn.12153. Epub 2013 Feb 13.
In the cerebral cortex of reeler mutant mice lacking reelin expression, neurons are malpositioned and display misoriented apical dendrites. Neuronal migration defects in reeler have been studied in great detail, but how misorientation of apical dendrites is related to reelin deficiency is poorly understood. In wild-type mice, the Golgi apparatus transiently translocates into the developing apical dendrite of radially migrating neurons. This dendritic Golgi translocation has recently been shown to be promoted by reelin. However, the underlying signalling mechanisms are largely unknown. Here, we show that the Cdc42/Rac1 guanine nucleotide exchange factor αPIX/Arhgef6 promoted translocation of Golgi cisternae into developing dendrites of hippocampal neurons. Reelin treatment further increased the αPIX-dependent effect. In turn, overexpression of exchange activity-deficient αPIX or dominant-negative (dn) Cdc42 or dn-Rac1 impaired dendritic Golgi positioning, an effect that was not compensated by reelin treatment. Together, these data suggest that αPIX may promote dendritic Golgi translocation, as a downstream component of a reelin-modulated signalling pathway. Finally, we found that reelin promoted the translocation of the Golgi apparatus into the dendrite that was most proximal to the reelin source. The distribution of reelin may thus contribute to the selection of the process that becomes the apical dendrite.
在缺乏 reelin 表达的 Reeler 突变小鼠的大脑皮层中，神经元位置错位，表现出定向错误的顶树突。Reeler 中的神经元迁移缺陷已经被深入研究，但顶树突的定向错误与 reelin 缺乏的关系还不太清楚。在野生型小鼠中，高尔基器在放射状迁移神经元的发育顶树突中短暂易位。最近的研究表明，reelin 促进了这种树突状高尔基易位。然而，其潜在的信号机制在很大程度上还不清楚。在这里，我们发现 Cdc42/Rac1 鸟嘌呤核苷酸交换因子 αPIX/Arhgef6 促进了高尔基潴腔向海马神经元发育树突的易位。reelin 处理进一步增强了 αPIX 依赖性效应。相反，过表达交换活性缺陷型 αPIX 或显性负性（dn）Cdc42 或 dn-Rac1 会损害树突状高尔基定位，而 reelin 处理不能补偿这种效应。总之，这些数据表明 αPIX 可能作为 reelin 调节的信号通路的下游成分，促进树突状高尔基易位。最后，我们发现 reelin 促进了高尔基器向离 reelin 源最近的树突的转位。reelin 的分布可能有助于选择成为顶树突的过程。
