A role for drosophila Drac1 in neurite outgrowth and synaptogenesis in the giant fiber system
A role for drosophila Drac1 in neurite outgrowth and synaptogenesis in the giant fiber system
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DOI：
10.1006/mcne.2000.0903
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发表时间：
2000-12-01
影响因子：
3.5
通讯作者：
Murphey, RK
中科院分区：
文献类型：
--
作者：
Allen, MJ;Shan, XL;Murphey, RK
最近的研究表明，小GTP酶，Rac 1，Rho和CDC 42，在轴突导向中发挥作用。为了评估它们参与突触组装和功能，我们在果蝇的巨纤维系统中表达了各种形式的Drac 1。野生型Drac 1在巨纤维（GF）中的过表达导致轴突形态的破坏;轴突通常在靶区的大肿胀处过早终止，但缺乏正常的外侧弯曲，在那里通常会发现与跳跃运动神经元的突触。电生理测定显示较长的潜伏期和较低的跟随频率，表明GF和背转子运动神经元之间的突触缺陷（TTMn）。在脑中也观察到增厚的异常GF树突。显性负性形式Drac 1（N17）的过表达导致在第二胸神经节（T2）中产生额外分支的轴突;然而，与TTMn的突触连接存在并且功能正常。相反，组成型活性形式Drac 1（V12）的表达导致完全缺乏神经突生长，这也见于Dcdc 42（V12）的过表达。在没有GF的情况下，这些果蝇在大脑刺激时在跳跃（TTM）或飞行（DLM）肌肉中没有反应。总之，这些结果表明，肌动蛋白聚合和解聚的平衡决定了局部过程的生长，从而突触的结构和功能。
Recent studies have shown the small GTPases, Rac1, Rho, and CDC42, to have a role in axon guidance. To assess their participation in synapse assembly and function we have expressed various forms of Drac1 in the giant fiber system of Drosophila. Overexpression of wildtype Drac1 in the giant fiber (GF) lead to a disruption in axonal morphology; axons often terminate prematurely in a large swelling in the target area but lack the normal lateral bend where the synapse with the jump motor neuron would normally be found. Electrophysiological assays revealed longer latencies and lowering following frequencies indicating defects in the synapse between the GF and the tergotrochanteral motor neuron (TTMn). Thickened abnormal GF dendrites were also observed in the brain. Overexpression of the dominant-negative form of Drac1, (N17), resulted in axons that produced extra branches in the second thoracic neuromere (T2); however, the synaptic connection to the TTMn was present and functioned normally. Conversely, expression of the constitutively active form, Drac1(V12), resulted in a complete lack of neurite outgrowth and this was also seen with overexpression of Dcdc42(V12). In the absence of a GF, these flies showed no response in the jump (TTM) or flight (DLM) muscles upon brain stimulation. Taken together these results show that the balance of actin polymerization and depolymerization determines local process outgrowth and thereby synapse structure and function.