Olenik C, Barth H, Just I, Aktories K, Meyer D K
Institut für Pharmakologie der Albert-Ludwigs-Universität Freiburg, Germany.
Brain Res Mol Brain Res. 1997 Dec 15;52(2):263-9. doi: 10.1016/s0169-328x(97)00270-2.
GTPases of the Rho subfamily, i.e. Rho, Rac and Cdc42, are molecular switches in various signaling pathways. Best characterized are their functions in the regulation of the actin cytoskeleton. In neuronal cell lines they are involved in the mechanisms leading to synapse formation and plasticity. It is still unknown whether they have respective functions in the mammalian CNS. In this case, they should be present in the adult brain, especially in areas known for their synaptic remodeling. We have studied the expression of the Rho GTPases in adult rat brain with in situ hybridization and Western blot analysis. High amounts of RhoA, RhoB, Rac1 and Cdc42 mRNAs were detected in neurons of the hippocampus, i.e. in pyramidal cells of the CA1-CA4 regions as well as in granule cells of the dentate gyrus and in hilar cells. Also in cerebellum, Purkinje and granular cells expressed the four mRNAs. Strong gene expression was also found in brainstem, thalamus and neocortex. Using Western blot analysis, RhoA and Cdc42 proteins were detected in hippocampus, cerebellum, thalamus and neocortex. It is concluded that GTPases of the Rho family play a role in the regulation of cellular functions in the adult brain.
Rho亚家族的GTP酶,即Rho、Rac和Cdc42,是各种信号通路中的分子开关。其在肌动蛋白细胞骨架调节中的功能得到了最充分的表征。在神经元细胞系中,它们参与了导致突触形成和可塑性的机制。它们在哺乳动物中枢神经系统中是否具有各自的功能仍不清楚。在这种情况下,它们应该存在于成年大脑中,尤其是在以突触重塑而闻名的区域。我们用原位杂交和蛋白质印迹分析研究了成年大鼠脑中Rho GTP酶的表达。在海马神经元中检测到大量的RhoA、RhoB、Rac1和Cdc42 mRNA,即在CA1-CA4区的锥体细胞以及齿状回的颗粒细胞和门区细胞中。在小脑中,浦肯野细胞和颗粒细胞也表达这四种mRNA。在脑干、丘脑和新皮层中也发现了强烈的基因表达。通过蛋白质印迹分析,在海马、小脑、丘脑和新皮层中检测到了RhoA和Cdc42蛋白。得出的结论是,Rho家族的GTP酶在成年大脑细胞功能的调节中发挥作用。