Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
PLoS Biol. 2013 Jul;11(7):e1001612. doi: 10.1371/journal.pbio.1001612. Epub 2013 Jul 23.
Body size in Drosophila larvae, like in other animals, is controlled by nutrition. Nutrient restriction leads to catabolic responses in the majority of tissues, but the Drosophila mitotic imaginal discs continue growing. The nature of these differential control mechanisms that spare distinct tissues from starvation are poorly understood. Here, we reveal that the Ret-like receptor tyrosine kinase (RTK), Stitcher (Stit), is required for cell growth and proliferation through the PI3K-I/TORC1 pathway in the Drosophila wing disc. Both Stit and insulin receptor (InR) signaling activate PI3K-I and drive cellular proliferation and tissue growth. However, whereas optimal growth requires signaling from both InR and Stit, catabolic changes manifested by autophagy only occur when both signaling pathways are compromised. The combined activities of Stit and InR in ectodermal epithelial tissues provide an RTK-mediated, two-tiered reaction threshold to varying nutritional conditions that promote epithelial organ growth even at low levels of InR signaling.
果蝇幼虫的体型与其他动物一样，受营养控制。营养限制会导致大多数组织发生分解代谢反应，但果蝇有丝分裂的 imaginal 盘仍会继续生长。这些使不同组织免受饥饿影响的差异控制机制的性质尚不清楚。在这里，我们揭示了 Ret 样受体酪氨酸激酶（RTK）Stitcher（Stit）通过果蝇翅膀盘的 PI3K-I/TORC1 途径，对于细胞生长和增殖是必需的。Stit 和胰岛素受体（InR）信号都激活了 PI3K-I，驱动细胞增殖和组织生长。然而，虽然最佳生长需要来自 InR 和 Stit 的信号，但只有当两条信号通路都受到损害时，才会出现自噬等分解代谢变化。Stit 和 InR 在表皮上皮组织中的联合活动为不同的营养条件提供了一种 RTK 介导的、两级反应阈值，即使在 InR 信号水平较低的情况下，也能促进上皮器官生长。
