Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany; Biotechnologisches Zentrum, Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307 Dresden, Germany.
Curr Biol. 2022 Apr 25;32(8):1788-1797.e5. doi: 10.1016/j.cub.2022.02.068. Epub 2022 Mar 21.
Insulin/insulin-like growth factor (IGF) signaling (IIS) controls many aspects of development and physiology. In Drosophila, a conserved family of insulin-like peptides called Dilps is produced by brain neurosecretory cells, and it regulates organismal growth and developmental timing. To accomplish these systemic functions, the Dilps are secreted into the general circulation, and they signal to peripheral tissues in an endocrine fashion. Here, we describe the local uptake and storage of Dilps in the corpora cardiaca (CC), an endocrine organ composed of alpha cell homologs known to produce the glucagon-like adipokinetic hormone (AKH). We show that Dilp uptake by the CC relies on the expression of an IGF-binding protein called ImpL2. Following their uptake, immunogold staining demonstrates that Dilps are co-packaged with AKH in dense-core vesicles for secretion. In response to nutrient shortage, this specific Dilp reservoir is released and activates IIS in a paracrine manner in the prothoracic gland. This stimulates the production of the steroid hormone ecdysone and initiates entry into pupal development. We therefore uncover a sparing mechanism whereby insulin stores in CC serve to locally activate IIS and the production of ecdysone in the PG, accelerating developmental progression in adverse food conditions.
胰岛素/胰岛素样生长因子（IGF）信号通路（IIS）控制着发育和生理的许多方面。在果蝇中，一种被称为 Dilps 的保守胰岛素样肽家族由脑神经分泌细胞产生，它调节着机体的生长和发育时间。为了完成这些系统功能，Dilps 被分泌到全身循环中，并以内分泌的方式向周围组织发出信号。在这里，我们描述了 Dilps 在心脏（CC）中的局部摄取和储存，CC 是由已知产生胰高血糖素样促肾上腺皮质激素（AKH）的α细胞同源物组成的内分泌器官。我们表明，CC 对 Dilp 的摄取依赖于一种叫做 ImpL2 的 IGF 结合蛋白的表达。在摄取之后，免疫金染色表明 Dilps 与 AKH 一起被包装在致密核心囊泡中进行分泌。在营养缺乏时，这个特定的 Dilp 储存库被释放出来，并以旁分泌的方式在前胸腺中激活 IIS，刺激类固醇激素蜕皮激素的产生，并启动进入蛹发育。因此，我们发现了一种节约机制，即 CC 中的胰岛素储存可以局部激活 IIS 和 PG 中蜕皮激素的产生，从而在不利的食物条件下加速发育进程。
