RACK1（Receptor for Activated C-Kinase 1）是一个在进化上高度保守的脚手架（Scaffold）蛋白，能通过WD40结构域与其他蛋白结合,从而参与多种细胞应激通路的调控。在哺乳动物胰岛β细胞中，RACK1在高糖刺激或内质网应激的状况下能够调节细胞内质网应激反应中IRE1蛋白的磷酸化，但是这一过程的生理学功能尚不明确。我们前期研究发现，在野生型果蝇中饥饿能诱导dRACK1的表达上调并激活dIRE1的磷酸化，提示dRACK1可能通过影响dIRE1的信号通路而发挥重要的生理学调节作用。本项目拟采用果蝇这一简单高效的遗传学模型，利用成熟的Gal4-UAS系统，在胰岛素分泌细胞群（IPCs）中特异性地过表达或将dRACK1和dIRE1敲减，在机体水平上开展遗传学相互作用的研究，探索RACK1在IPC中的生理学功能及其作用机制，从而了解RACK1如何通过调控内质网 。

RACK1, a scaffold protein containing seven Trp-Asp 40 (WD 40) repeats, can bind to activated proteins and coordinate the interactions between signaling components in mutiple cellular processes. In pancreatic β-cells, RACK1 has been shown to regulate the phosphorylation of IRE1α, an ancient ER stress sensor, in response to glucose stimulation or ER stress conditions. However, the exact physiological function of RACK1 remains largely elusive. We have found that in the fruitfly Drosophila, starvation could increase the expression of dRACK1 as well as the phosphorylation level of dIRE1. Therefore, we intend to investigate the physiolgical role of RACK1 in the insulin producing cells (IPCs) of Drosophila. Through generating fly lines with IPC-specific overexpression or knockdown of dRACK1 and dIRE1 via the Gal4-UAS system, we aim to perform genetic interaction studies to examine the physiological functions of dRACK1 in growth, metabolism and longevity. Our study will provide new insights into the molecular evolution of RACK1 regulation of the ER stress signaling pathway in the context of metabolic dysfunctions.