Anaplastic Lymphoma Kinase Spares Organ Growth during Nutrient Restriction in Drosophila
Anaplastic Lymphoma Kinase Spares Organ Growth during Nutrient Restriction in Drosophila
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DOI：
10.1016/j.cell.2011.06.040
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发表时间：
2011-08-05
期刊：
影响因子：
64.5
通讯作者：
Gould, Alex P.
中科院分区：
文献类型：
--
作者：
Cheng, Louise Y.;Bailey, Andrew P.;Gould, Alex P.
发育中的动物通过牺牲其他组织来保护重要器官的生长，从而在饥饿时期生存下来。在这里，我们使用果蝇来探索尚未未知的机制，调节这种特权组织的生长。与哺乳动物一样，我们在果蝇中观察到，在营养限制（NR）期间，CNS比其他组织更高。我们证明，间变性淋巴瘤激酶（ALK）有效地保护神经祖细胞（神经母细胞）的生长，通过两种机制，对减少氨基酸和胰岛素样肽在NR。首先，Alk通过Slimfast/Rheb/TOR复合物1抑制氨基酸传感的生长需求。其次，Alk而不是胰岛素样受体主要激活PI 3激酶。ALK在NR期间维持PI 3-激酶信号传导，因为其配体Jelly belly（Jeb）从成神经细胞周围的胶质细胞龛组成性表达。总之，这些发现确定了一种脑保护机制，该机制与哺乳动物肿瘤的耐饥饿生长程序共享一些调控特征。
Developing animals survive periods of starvation by protecting the growth of critical organs at the expense of other tissues. Here, we use Drosophila to explore the as yet unknown mechanisms regulating this privileged tissue growth. As in mammals, we observe in Drosophila that the CNS is more highly spared than other tissues during nutrient restriction (NR). We demonstrate that anaplastic lymphoma kinase (Alk) efficiently protects neural progenitor (neuroblast) growth against reductions in amino acids and insulin-like peptides during NR via two mechanisms. First, Alk suppresses the growth requirement for amino acid sensing via Slimfast/Rheb/TOR complex 1. And second, Alk, rather than insulin-like receptor, primarily activates PI3-kinase. Alk maintains PI3-kinase signaling during NR as its ligand, Jelly belly (Jeb), is constitutively expressed from a glial cell niche surrounding neuroblasts. Together, these findings identify a brain-sparing mechanism that shares some regulatory features with the starvation-resistant growth programs of mammalian tumors.