Luo L, Hensch T K, Ackerman L, Barbel S, Jan L Y, Jan Y N
Howard Hughes Medical Institute, Department of Physiology, University of California at San Francisco, 94143, USA.
Nature. 1996 Feb 29;379(6568):837-40. doi: 10.1038/379837a0.
Neurons contain distinct compartments including dendrites, dendritic spines, axons and synaptic terminals. The molecular mechanisms that generate and distinguish these compartments, although largely unknown, may involve the small GTPases Rac and Cdc42, which appear to regulate actin polymerization. Having shown that perturbations of Rac1 activity block the growth of axons but not dendrites of Drosophila neurons, we investigated whether this also applies to mammals by examining transgenic mice expressing constitutively active human Rac1 in Purkinje cells. We found that these mice were ataxic and had a reduction of Purkinje-cell axon terminals in the deep cerebellar nuclei, whereas the dendritic trees grew to normal height and branched extensively. Unexpectedly, the dendritic spines of Purkinje cells in developing and mature cerebella were much reduced in size but increased in number. These 'mini' spines often form supernumerary synapses. These differential effects of perturbing Rac1 activity indicate that there may be distinct mechanisms for the elaboration of axons, dendrites and dendritic spines.
神经元包含不同的区室，包括树突、树突棘、轴突和突触终末。尽管在很大程度上尚不清楚，但产生和区分这些区室的分子机制可能涉及小GTP酶Rac和Cdc42，它们似乎调节肌动蛋白聚合。在已证明Rac1活性的扰动会阻断果蝇神经元轴突的生长但不影响树突的生长后，我们通过检查在浦肯野细胞中组成型表达活性人Rac1的转基因小鼠，研究了这是否也适用于哺乳动物。我们发现这些小鼠共济失调，并且小脑深部核团中浦肯野细胞轴突终末减少，而树突树生长到正常高度并广泛分支。出乎意料的是，发育中和成熟小脑中浦肯野细胞的树突棘尺寸大幅减小但数量增加。这些“微型”树突棘常常形成多余的突触。扰动Rac1活性的这些不同效应表明，轴突、树突和树突棘的形成可能存在不同的机制。
