Mizui Toshiyuki, Kojima Nobuhiko, Yamazaki Hiroyuki, Katayama Michihito, Hanamura Kenji, Shirao Tomoaki
Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Japan.
J Neurochem. 2009 Apr;109(2):611-22. doi: 10.1111/j.1471-4159.2009.05993.x. Epub 2009 Feb 13.
Drebrin is a well-known side-binding protein of F-actin in the brain. Immunohistochemical data suggest that the peripheral parts of growing axons are enriched in the drebrin E isoform and mature axons are not. It has also been observed that drebrin E is concentrated in the growth cones of PC12 cells. These data strongly suggest that drebrin E plays a role in axonal growth during development. In this study, we used primary hippocampal neuronal cultures to analyze the role of drebrin E. Immunocytochemistry showed that within axonal growth cones drebrin E specifically localized to the transitional zone, an area in which dense networks of F-actins and microtubules overlapped. Over-expression of drebrin E caused drebrin E and F-actin to accumulate throughout the growth cone and facilitated axonal growth. In contrast, knockdown of drebrin E reduced drebrin E and F-actin in the growth cone and prevented axonal growth. Furthermore, inhibition of myosin II ATPase masked the promoting effects of drebrin E over-expression on axonal growth. These results suggest that drebrin E plays a role in axonal growth through actin-myosin interactions in the transitional zone of axonal growth cones.
双调蛋白是大脑中一种著名的F-肌动蛋白侧结合蛋白。免疫组织化学数据表明,正在生长的轴突外周部分富含双调蛋白E亚型,而成熟轴突中则没有。还观察到双调蛋白E集中在PC12细胞的生长锥中。这些数据有力地表明,双调蛋白E在发育过程中的轴突生长中发挥作用。在本研究中,我们使用原代海马神经元培养物来分析双调蛋白E的作用。免疫细胞化学显示,在轴突生长锥内,双调蛋白E特异性定位于过渡区,即F-肌动蛋白和微管密集网络重叠的区域。双调蛋白E的过表达导致双调蛋白E和F-肌动蛋白在整个生长锥中积累,并促进轴突生长。相反,双调蛋白E的敲低减少了生长锥中的双调蛋白E和F-肌动蛋白,并阻止了轴突生长。此外,肌球蛋白II ATP酶的抑制掩盖了双调蛋白E过表达对轴突生长的促进作用。这些结果表明,双调蛋白E通过轴突生长锥过渡区的肌动蛋白-肌球蛋白相互作用在轴突生长中发挥作用。