Department of Anatomy, School of Medical Sciences, University of New South Wales, NSW, Australia.
Eur J Cell Biol. 2010 Jul;89(7):489-98. doi: 10.1016/j.ejcb.2009.11.028. Epub 2010 Mar 12.
Previous studies have shown that the overexpression of tropomyosins leads to isoform-specific alterations in the morphology of subcellular compartments in neuronal cells. Here we have examined the role of the most abundant set of isoforms from the gamma-Tm gene by knocking out the alternatively spliced C-terminal exon 9d. Despite the widespread location of exon 9d-containing isoforms, mice were healthy and viable. Compensation by products containing the C-terminal exon 9c was seen in the adult brain. While neurons from these mice show a mild phenotype at one day in culture, neurons revealed a significant morphological alteration with an increase in the branching of dendrites and axons after four days in culture. Our data suggest that this effect is mediated via altered stability of actin filaments in the growth cones. We conclude that exon 9d-containing isoforms are not essential for survival of neuronal cells and that isoform choice from the gamma-Tm gene is flexible in the brain. Although functional redundancy does not exist between tropomyosin genes, these results suggest that significant redundancy exists between products from the same gene.
先前的研究表明，原肌球蛋白的过表达会导致神经元细胞亚细胞区室形态的同工型特异性改变。在这里，我们通过敲除交替剪接的 C 端外显子 9d 来研究最丰富的γ-Tm 基因同工型的作用。尽管含有外显子 9d 的同工型广泛存在，但小鼠仍然健康且具有活力。在成年大脑中观察到含有 C 端外显子 9c 的产物的补偿。尽管来自这些小鼠的神经元在培养的第一天表现出轻微的表型，但在培养四天后，神经元显示出明显的形态改变，树突和轴突的分支增加。我们的数据表明，这种效应是通过生长锥中肌动蛋白丝稳定性的改变来介导的。我们得出结论，含有外显子 9d 的同工型对于神经元细胞的存活不是必需的，并且来自γ-Tm 基因的同工型选择在大脑中是灵活的。尽管原肌球蛋白基因之间不存在功能冗余，但这些结果表明，来自同一基因的产物之间存在显著的冗余。
