Protein serine/threonine Phosphotase-2A is differentially expressed and regulates eye development in vertebrates.
Protein serine/threonine Phosphotase-2A is differentially expressed and regulates eye development in vertebrates.
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DOI：
10.2174/15665240113139990061
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发表时间：
2013-08
影响因子：
2.5
通讯作者：
W-b Liu;X-H Hu;X-W Zhang;M. Deng;L. Nie;S. Hui;W. Duan;M. Tao;C. Zhang;J. Liu;W-F Hu;Z-X Huang;L. Li;M. Yi;T-T Li-T;L. Wang;Y. Liu;S. Liu;D. W. Li
中科院分区：
文献类型：
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作者：
W-b Liu;X-H Hu;X-W Zhang;M. Deng;L. Nie;S. Hui;W. Duan;M. Tao;C. Zhang;J. Liu;W-F Hu;Z-X Huang;L. Li;M. Yi;T-T Li-T;L. Wang;Y. Liu;S. Liu;D. W. Li
蛋白丝氨酸/苏氨酸磷酸酶-2A（PP-2A）是脊椎动物体内负责去磷酸化的关键酶之一。PP-2A介导的去磷酸化参与了许多不同的生物学过程，包括细胞增殖、分化、转化、凋亡、自噬和衰老。然而，PP-2A是否直接控制动物发育仍有待探索。在这里，我们提出了直接的证据表明，PP-2A显示在调节脊椎动物的眼睛发育的重要功能。使用金鱼作为模型系统，我们已经证明了以下新颖的信息。首先，PP-2A活性的抑制导致经处理的胚胎的显著死亡，这源自与Bcl-XL在Ser-62处的磷酸化增强相关的卵裂球凋亡，并且存活的胚胎在眼睛中显示严重的表型。第二，用吗啉代寡聚体敲低PP-2A导致注射的胚胎显著死亡。PP-2A敲除后的存活胚胎在透镜分化中表现出明显的延迟。最后，PP-2A的每个催化亚基的过表达也会导致大多数注射胚胎的死亡，并导致金鱼眼透镜的缺失或严重干扰分化。总之，我们的研究结果提供了直接的证据表明，蛋白磷酸酶-2A对金鱼的正常眼睛发育很重要。
Protein serine/threonine phosphatase-2A (PP-2A) is one of the key enzymes responsible for dephosphorylation in vertebrates. PP-2A-mediated dephosphorylation participates in many different biological processes including cell proliferation, differentiation, transformation, apoptosis, autophage and senescence. However, whether PP-2A directly controls animal development remains to be explored. Here, we present direct evidence to show that PP-2A displays important functions in regulating eye development of vertebrates. Using goldfish as a model system, we have demonstrated the following novel information. First, inhibition of PP-2A activity leads to significant death of the treated embryos, which is derived from blastomere apoptosis associated with enhanced phosphorylation of Bcl-XL at Ser-62, and the survived embryos displayed severe phenotype in the eye. Second, knockdown of PP-2A with morpholino oligomers leads to significant death of the injected embryos. The survived embryos from PP-2A knockdown displayed clear retardation in lens differentiation. Finally, overexpression of each catalytic subunit of PP-2A also causes death of majority of the injected embryos and leads to absence of goldfish eye lens or severely disturbed differentiation. Together, our results provide direct evidence that protein phosphatase-2A is important for normal eye development in goldfish.