Rab5 and Rab11 maintain hematopoietic homeostasis by restricting multiple signaling pathways in Drosophila.
Rab5 and Rab11 maintain hematopoietic homeostasis by restricting multiple signaling pathways in Drosophila.
复制标题
Rab5 和 Rab11 通过限制果蝇中的多种信号通路维持造血稳态
作者：
Yu S;Luo F;Jin LH
果蝇的造血系统是研究造血的一个强大的遗传模型，囊泡运输是重要的信号转导在各种发育过程中，然而，它与造血的相互作用目前在很大程度上是未知的。在这篇文章中，我们选择了三个内体标记物Rab 5，Rab 7和Rab 11，它们在膜运输中起关键作用，并确定它们是否参与造血。在血细胞或皮质区（CZ）中抑制Rab 5或Rab 11可显著诱导循环血细胞和淋巴腺中的细胞过度增殖和板层细胞形成，并破坏血细胞祖细胞的维持。板层细胞的形成涉及JNK、Toll和Ras/EGFR信号通路。值得注意的是，板层细胞形成也与JNK依赖性自噬相关。总之，我们确定Rab 5和Rab 11作为新的造血调节因子，我们的研究结果促进了对维持造血稳态的机制以及血液疾病（如白血病）病理学的理解。
The hematopoietic system of Drosophila is a powerful genetic model for studying hematopoiesis, and vesicle trafficking is important for signal transduction during various developmental processes; however, its interaction with hematopoiesis is currently largely unknown. In this article, we selected three endosome markers, Rab5, Rab7, and Rab11, that play a key role in membrane trafficking and determined whether they participate in hematopoiesis. Inhibiting Rab5 or Rab11 in hemocytes or the cortical zone (CZ) significantly induced cell overproliferation and lamellocyte formation in circulating hemocytes and lymph glands and disrupted blood cell progenitor maintenance. Lamellocyte formation involves the JNK, Toll, and Ras/EGFR signaling pathways. Notably, lamellocyte formation was also associated with JNK-dependent autophagy. In conclusion, we identified Rab5 and Rab11 as novel regulators of hematopoiesis, and our results advance the understanding of the mechanisms underlying the maintenance of hematopoietic homeostasis as well as the pathology of blood disorders such as leukemia.