Autophagic dedifferentiation induced by cooperation between TOR inhibitor and retinoic acid signals in budding tunicates
Autophagic dedifferentiation induced by cooperation between TOR inhibitor and retinoic acid signals in budding tunicates
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DOI：
10.1016/j.ydbio.2017.08.023
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发表时间：
2018-01-15
影响因子：
2.7
通讯作者：
Sekida, Satoko
中科院分区：
文献类型：
--
作者：
Kawamura, Kaz;Yoshida, Takuto;Sekida, Satoko
在出芽被囊Polyandrocarpa misakiensis的无性芽发育涉及转分化的多能上皮细胞，这是由视黄酸（RA）触发，并在饥饿下茁壮成长芽隔离从父母。本研究旨在确定转分化早期发生的去分化的细胞和分子机制。在去分化过程中，自噬体、溶酶体和次级溶酶体的数量显著增加。线粒体降解和外泌体放电也发生在心房上皮。自噬相关基因7（Atg 7）和溶酶体质子泵A基因（PumpA）在去分化期被激活。当雷帕霉素（TOR）抑制剂的目标管理生长芽，而不将它们从父母，吞噬体和次级溶酶体变得突出。TOR抑制剂仅在RA存在下诱导Atg7。相反，当生长芽用RA处理时，溶酶体、次级溶酶体和线粒体降解被过早地诱导。RA以视黄酸X受体依赖的方式显著激活PumpA。我们的研究结果表明，在P. misakiensis中，TOR抑制和RA信号协同作用，以完成去分化的细胞质清除。
Asexual bud development in the budding tunicate Polyandrocarpa misakiensis involves transdifferentiation of multipotent epithelial cells, which is triggered by retinoic acid (RA), and thrives under starvation after bud isolation from the parent. This study aimed to determine cell and molecular mechanisms of dedifferentiation that occur during the early stage of transdifferentiation. During dedifferentiation, the numbers of autophagosomes, lysosomes, and secondary lysosomes increased remarkably. Mitochondrial degradation and exosome discharge also occurred in the atrial epithelium. Autophagy-related gene 7 (Atg7) and lysosomal proton pump A gene (PumpA) were activated during the dedifferentiation stage. When target of rapamycin (TOR) inhibitor was administered to growing buds without isolating them from the parent, phagosomes and secondary lysosomes became prominent. TOR inhibitor induced Atg7 only in the presence of RA. In contrast, when growing buds were treated with RA, lysosomes, secondary lysosomes, and mitochondrial degradation were prematurely induced. RA significantly activated PumpA in a retinoid X receptor-dependent manner. Our results indicate that in P. misakiensis, TOR inhibition and RA signals act in synergy to accomplish cytoplasmic clearance for dedifferentiation.