Developmental Neurobiology Unit, Okinawa Institute of Science and Technology (OIST), Onna, Okinawa, Japan.
Development. 2010 Oct;137(19):3257-68. doi: 10.1242/dev.053124. Epub 2010 Aug 19.
In the developing vertebrate lens, epithelial cells differentiate into fiber cells, which are elongated and flat in shape and form a multilayered lens fiber core. In this study, we identified the zebrafish volvox (vov) mutant, which shows defects in lens fiber differentiation. In the vov mutant, lens epithelial cells fail to proliferate properly. Furthermore, differentiating lens fiber cells do not fully elongate, and the shape and position of lens fiber nuclei are affected. We found that the vov mutant gene encodes Psmd6, the subunit of the 26S proteasome. The proteasome regulates diverse cellular functions by degrading polyubiquitylated proteins. Polyubiquitylated proteins accumulate in the vov mutant. Furthermore, polyubiquitylation is active in nuclei of differentiating lens fiber cells, suggesting roles of the proteasome in lens fiber differentiation. We found that an E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is involved in lens defects in the vov mutant. These data suggest that the ubiquitin proteasome system is required for cell proliferation of lens epithelium and for the differentiation of lens fiber cells in zebrafish.
在脊椎动物晶状体的发育过程中，上皮细胞分化为纤维细胞，纤维细胞呈长而扁的形状，并形成多层晶状体纤维核心。在这项研究中，我们鉴定了斑马鱼 volvox（vov）突变体，其表现出晶状体纤维分化缺陷。在 vov 突变体中，晶状体上皮细胞不能正常增殖。此外，分化的晶状体纤维细胞不能完全伸长，晶状体纤维细胞核的形状和位置受到影响。我们发现 vov 突变体基因编码 Psmd6，这是 26S 蛋白酶体的亚基。蛋白酶体通过降解多泛素化蛋白来调节多种细胞功能。在 vov 突变体中，多泛素化蛋白积累。此外，多泛素化在分化的晶状体纤维细胞核中活跃，表明蛋白酶体在晶状体纤维分化中起作用。我们发现，一种 E3 泛素连接酶有丝分裂促进复合物/周期蛋白（APC/C）参与了 vov 突变体的晶状体缺陷。这些数据表明，泛素蛋白酶体系统对于晶状体上皮细胞的增殖和斑马鱼晶状体纤维细胞的分化是必需的。
