The ubiquitin proteasome system is required for cell proliferation of the lens epithelium and for differentiation of lens fiber cells in zebrafish
The ubiquitin proteasome system is required for cell proliferation of the lens epithelium and for differentiation of lens fiber cells in zebrafish
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DOI：
10.1242/dev.053124
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发表时间：
2010-10-01
期刊：
影响因子：
4.6
通讯作者：
Masai, Ichiro
中科院分区：
文献类型：
--
作者：
Imai, Fumiyasu;Yoshizawa, Asuka;Masai, Ichiro
在发育中的脊椎动物晶状体中，上皮细胞分化为纤维细胞，纤维细胞呈细长扁平状，形成多层晶状体纤维核。在这项研究中，我们鉴定了斑马鱼volvox （vov）突变体，该突变体在晶状体纤维分化方面存在缺陷。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，晶状体纤维核的形状和位置受到影响。我们发现vov突变基因编码26S蛋白酶体的亚基Psmd6。蛋白酶体通过降解多泛素化蛋白调节多种细胞功能。多泛素化蛋白在vov突变体中积累。此外，多泛素化在晶状体纤维细胞的分化细胞核中很活跃，提示蛋白酶体在晶状体纤维分化中的作用。我们发现E3泛素连接酶后期促进复合体/环体（APC/C）参与了vov突变体的晶体缺陷。这些数据表明，泛素蛋白酶体系统是斑马鱼晶状体上皮细胞增殖和晶状体纤维细胞分化所必需的。
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.