Farrar Nathan R, Dmetrichuk Jennifer M, Carlone Robert L, Spencer Gaynor E
Department Biological Sciences, Brock University, St. Catharines, Ontario L2S 3A1, Canada.
J Neurosci. 2009 Nov 11;29(45):14136-42. doi: 10.1523/JNEUROSCI.2921-09.2009.
The vitamin A metabolite, retinoic acid (RA), is well known for its roles in neural development and regeneration. We have previously shown that RA can induce positive growth cone turning in regenerating neurons in vitro. In this study, we address the subcellular mechanisms underlying this chemo-attractive response, using identified central neurons from the adult mollusc, Lymnaea stagnalis. We show that the RA-induced positive growth cone turning was maintained in the presence of the transcriptional inhibitor, actinomycin D. We also physically transected the neurites from the cell body and showed that isolated growth cones retain the capacity to turn toward a gradient of RA. Moreover, this attractive turning is dependent on de novo local protein synthesis and Ca(2+) influx. Most of RA's actions during neurite outgrowth and regeneration require gene transcription, although these data show for the first time in any species, that the chemotropic action of RA in guiding neurite outgrowth, involves a novel, nongenomic mechanism.
维生素A代谢产物视黄酸（RA）在神经发育和再生中的作用广为人知。我们之前已经表明，RA能够在体外诱导再生神经元的生长锥发生正向转向。在本研究中，我们利用成年软体动物椎实螺已鉴定的中枢神经元，探讨了这种化学吸引反应背后的亚细胞机制。我们发现，在存在转录抑制剂放线菌素D的情况下，RA诱导的生长锥正向转向依然能够维持。我们还从细胞体上物理切断神经突，结果显示分离出的生长锥保留了向RA梯度转向的能力。此外，这种吸引性转向依赖于从头开始的局部蛋白质合成和Ca(2+)内流。尽管这些数据首次在任何物种中表明，RA在引导神经突生长中的化学趋向作用涉及一种新的非基因组机制，但RA在神经突生长和再生过程中的大多数作用都需要基因转录。
