Kirkland Rebecca A, Franklin James L
Department of Pharmaceutical and Biomedical Sciences, The University of Georgia College of Pharmacy, 357 Wilson Pharmacy, Athens, Georgia 30602, United States.
Neurosci Lett. 2007 Jan 3;411(1):52-5. doi: 10.1016/j.neulet.2006.10.045. Epub 2006 Nov 16.
Neurites projecting to their target tissues during embryogenesis are subject to many perturbations that could influence their rate of growth. For example, environmental influences such as supply of neurotrophic factor or electrical activity profoundly influence the rate of neuronal protein synthesis. Because accumulation of protein is necessary for outgrowth to proceed normally, a perturbation in protein synthesis could cause a net change in the rate of accumulation of proteins with the result that neurite outgrowth rate increases or decreases. That neurite outgrowth does not normally seem to be subject to such perturbations suggests involvement of a homeostatic system controlling the rate of outgrowth. Consistent with this hypothesis, we show here that the rate of growth of neurites of sympathetic neurons is highly resistant to decreased rates of protein synthesis. Chronic suppression of protein synthesis by 60% had no significant effect on neurite outgrowth over a 2-day period while complete suppression halted it almost immediately. By the 3rd day of exposure, 60% suppression slowed outgrowth. Sustained suppression of protein synthesis rate by 33% had no effect on rate of outgrowth even after 7 days. We show that the ability of the growing neurites to resist protein synthesis suppression appears to be caused, at least in part, by a parallel decrease in the rate of protein degradation. The result of this coupling between degradation and synthesis is that proteins can continue to accumulate even when protein synthesis rate decreases, allowing normal rates of neurite outgrowth.
在胚胎发育过程中，向其靶组织投射的神经突会受到许多可能影响其生长速度的干扰。例如，神经营养因子供应或电活动等环境影响会深刻影响神经元蛋白质合成的速度。由于蛋白质的积累是神经突正常生长所必需的，蛋白质合成的干扰可能会导致蛋白质积累速度的净变化，结果是神经突生长速度增加或降低。神经突生长通常似乎不受此类干扰的影响，这表明存在一个控制生长速度的稳态系统。与这一假设一致，我们在此表明，交感神经元神经突的生长速度对蛋白质合成速度的降低具有高度抗性。蛋白质合成长期抑制60%在2天内对神经突生长没有显著影响，而完全抑制几乎立即停止神经突生长。到暴露的第3天，60%的抑制减缓了神经突生长。即使在7天后，蛋白质合成速度持续抑制33%对神经突生长速度也没有影响。我们表明，生长中的神经突抵抗蛋白质合成抑制的能力似乎至少部分是由蛋白质降解速度的平行降低引起的。降解与合成之间这种耦合的结果是，即使蛋白质合成速度降低，蛋白质仍能继续积累，从而使神经突正常生长。
