Activation of the cAMP/PKA signaling pathway is required for post-ecdysial cell death in wing epidermal cells of Drosophila melanogaster
Activation of the cAMP/PKA signaling pathway is required for post-ecdysial cell death in wing epidermal cells of Drosophila melanogaster
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DOI：
10.1242/dev.01049
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发表时间：
2004-04-01
期刊：
影响因子：
4.6
通讯作者：
Ohta, T
中科院分区：
文献类型：
--
作者：
Kimura, KI;Kodama, A;Ohta, T
在果蝇变态的最后阶段，在羽化后的展翅行为中，翅表皮细胞通过程序性细胞死亡而被去除。TUNEL法显示细胞死亡伴随着DNA断裂。透射电子显微镜显示，这种细胞死亡表现出广泛的空泡，表明自噬。异位表达的抗凋亡基因，p35，抑制细胞死亡，表明参与半胱天冬酶。颈结扎和血淋巴注射实验表明，细胞死亡是由羽化后分泌的激素因子触发的。激素释放的时间意味着引发死亡的激素可能是昆虫晒黑激素，bursicon。这得到了证据的支持，翼细胞死亡被抑制的突变的门票，它编码的G蛋白偶联受体的糖蛋白激素家族，是一个假定的bursicon受体。此外，刺激bursicon下游的组分，如cAMP的膜渗透类似物，或G蛋白或PKA的组成型活性形式的异位表达，诱导早熟死亡。相反，在缺乏G蛋白或PKA功能的翅克隆中，细胞死亡被抑制。因此，激活cAMP/PKA信号通路是诱导羽化后翅表皮细胞死亡的激素信号转导所必需的。
At the last step of metamorphosis in Drosophila, the wing epidermal cells are removed by programmed cell death during the wing spreading behavior after eclosion. The cell death was accompanied by DNA fragmentation demonstrated by the TUNEL assay. Transmission electron microscopy revealed that this cell death exhibited extensive vacuoles, indicative of autophagy. Ectopic expression of an anti-apoptotic gene, p35, inhibited the cell death, indicating the involvement of caspases. Neck ligation and hemolymph injection experiments demonstrated that the cell death is triggered by a hormonal factor secreted just after eclosion. The timing of the hormonal release implies that the hormone to trigger the death might be the insect tanning hormone, bursicon. This was supported by evidence that wing cell death was inhibited by a mutation of tickets, which encodes a G-protein coupled receptor in the glycoprotein hormone family that is a putative bursicon receptor. Furthermore, stimulation of components downstream of bursicon, such as a membrane permeant analog of cAMP, or ectopic expression of constitutively active forms of G proteins or PKA, induced precocious death. Conversely, cell death was inhibited in wing clones lacking G protein or PKA function. Thus, activation of the cAMP/PKA signaling pathway is required for transduction of the hormonal signal that induces wing epidermal cell death after eclosion.