Bolis Annalisa, Corbetta Sara, Cioce Antonella, de Curtis Ivan
Cell Adhesion Unit, Department of Molecular Biology and Functional Genomics, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
Eur J Neurosci. 2003 Nov;18(9):2417-24. doi: 10.1046/j.1460-9568.2003.02938.x.
Rac3 is one of the three known Rac GTPases in vertebrates. Rac3 shows high sequence homology to Rac1, and its transcript is specifically expressed in the developing nervous system, where its localization and function are unknown. By using Rac3-specific antibodies, we show that the endogenous Rac3 protein is differentially expressed during mouse brain development, with a peak of expression at times of neuronal maturation and synaptogenesis. Comparison with Rac1 shows clear-cut differences in the overall distribution of the two GTPases in the developing brain, and in their subcellular distribution in regions of the brain where both proteins are expressed. At P7, Rac3 staining is particularly marked in the deep cerebellar nuclei and in the pons, where it shows a discontinuous distribution around the neuronal cell bodies, in contrast with the diffuse staining of Rac1. Rac3 does not evidently co-localize with pre- and post-synaptic markers, nor with GFAP-positive astrocytes, but it clearly co-localizes with actin filaments, and with the terminal portions of calbindin-positive Purkinje cell axons in the deep cerebellar nuclei. Our data implicate Rac3 in neuronal differentiation, and support a specific role of this GTPase in actin-mediated remodelling of Purkinje cell neuritic terminals at time of synaptogenesis.
Rac3是脊椎动物中已知的三种Rac GTP酶之一。Rac3与Rac1具有高度的序列同源性，其转录本在发育中的神经系统中特异性表达，但其定位和功能尚不清楚。通过使用Rac3特异性抗体，我们发现内源性Rac3蛋白在小鼠脑发育过程中差异表达，在神经元成熟和突触形成时表达达到峰值。与Rac1的比较表明，这两种GTP酶在发育中的大脑中的整体分布以及在两种蛋白均表达的脑区中的亚细胞分布存在明显差异。在出生后第7天（P7），Rac3染色在小脑深部核团和脑桥中尤为明显，在神经元细胞体周围呈间断分布，这与Rac1的弥漫性染色形成对比。Rac3与突触前和突触后标记物以及GFAP阳性星形胶质细胞均无明显共定位，但它与肌动蛋白丝以及小脑深部核团中钙结合蛋白阳性浦肯野细胞轴突的末端部分明显共定位。我们的数据表明Rac3参与神经元分化，并支持这种GTP酶在突触形成时对浦肯野细胞神经突末端肌动蛋白介导的重塑中发挥特定作用。
