HSP90 function is required for morphogenesis in ascidian and echinoid embryos
HSP90 function is required for morphogenesis in ascidian and echinoid embryos
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DOI：
10.1007/s00427-002-0212-9
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发表时间：
2002-03-01
影响因子：
2.4
通讯作者：
Brandhorst, BP
中科院分区：
文献类型：
--
作者：
Bishop, CD;Bates, WR;Brandhorst, BP
用抗HSP90药物格尔达那霉素和自由基酚处理簇毛海鞘、海胆和紫球海胆的胚胎可引起形态发生停滞。观察到明显形态发生的所有胚胎阶段都对处理敏感，包括海胆胚泡上皮的形成。停滞的胚胎在治疗后几个小时到几天都能存活，这表明这些药物的总体毒性很低。海胆初级和次级间充质细胞的形态发生运动，包括原肠形成和迁移(而不是内移)，在治疗开始后8-10h停止。形态发生停止后，细胞分裂和某些基因的发育调控表达仍在继续。抗HSP90药物导致与HSP90蛋白伴侣相互作用的蛋白质选择性失活或降解。因此，HSP90功能中断后的形态发生停滞可能是由于细胞形态发生运动所需的客户蛋白的浓度或活性降低所致。这些药物的使用可能会提供一种手段来识别与形态发生有关的新活性或蛋白质。
Treatment of embryos of the ascidians Boltenia villosa and Cnemidocarpa finmarkiensis and the sea urchin Strongylocentrotus purpuratus with the anti-HSP90 drugs geldanamycin and radicicol caused morphogenetic arrest. All embryonic stages during which obvious morphogenesis was observed were sensitive to treatment, including formation of the sea urchin blastular epithelium. Arrested embryos were viable for many hours to days post-treatment, indicating a low general toxicity of these drugs. Morphogenetic movements including gastrulation and migration (but not ingression) of sea urchin primary and secondary mesenchyme cells were arrested 8-10 h after treatment began. Cell division and developmentally regulated expression of some genes continued after morphogenesis was arrested. Anti-HSP90 drugs cause selective inactivation or degradation of proteins with which the protein chaperone HSP90 interacts. Therefore, morphogenetic arrest subsequent to the disruption of HSP90 function may result from the reduction in concentration, or activity, of client proteins required for morphogenetic movements of cells. The use of these drugs may provide a means to identify novel activities or proteins involved in morphogenesis.