Yuan Li, Cao Ying, Knöchel Walter
Institute of Biochemistry, University of Ulm, Ulm, Germany.
Dev Dyn. 2007 Oct;236(10):2844-51. doi: 10.1002/dvdy.21299.
Maintenance of endoplasmic reticulum (ER) homeostasis is essential for correct protein targeting and secretion. ER stress caused by accumulation of unfolded or misfolded proteins leads to disruption of cellular functions. We have investigated the effect of ER stress on Xenopus embryogenesis. ER stress induced by tunicamycin (TM) treatment of embryos resulted in defects affecting germ layer formation. We observed up-regulation of ER stress response genes, enhanced cytoplasmic splicing of xXBP1 RNA, and increased rate of apoptosis. In animal cap assays, TM treatment inhibited mesoderm formation induced by overexpression of activin/nodal RNA but did not affect mesoderm formation induced by functional activin protein, suggesting that dysfunction of ER caused a failure in activin/nodal processing and/or secretion. The observation that activin protein renders mesoderm formation under ER stress strengthens the role of activin/nodal for mesoderm induction. The results underline the functional significance of ER homeostasis in germ layer formation during Xenopus embryogenesis.
内质网（ER）稳态的维持对于正确的蛋白质靶向和分泌至关重要。未折叠或错误折叠蛋白质的积累所导致的内质网应激会导致细胞功能紊乱。我们研究了内质网应激对非洲爪蟾胚胎发育的影响。用衣霉素（TM）处理胚胎诱导的内质网应激导致影响胚层形成的缺陷。我们观察到内质网应激反应基因上调、xXBP1 RNA的细胞质剪接增强以及凋亡率增加。在动物帽实验中，TM处理抑制了由激活素/节点RNA过表达诱导的中胚层形成，但不影响由功能性激活素蛋白诱导的中胚层形成，这表明内质网功能障碍导致激活素/节点加工和/或分泌失败。激活素蛋白在内质网应激下促使中胚层形成这一观察结果强化了激活素/节点在中胚层诱导中的作用。这些结果强调了内质网稳态在非洲爪蟾胚胎发育过程中胚层形成中的功能意义。
