DFG WEAVE
Identification of a Golgi quality control network
The Golgi apparatus plays a central role in protein sorting and proteostasis, but its quality control (QC) mechanisms remain poorly understood. Recent work identified the Dsc ubiquitin ligase complex as a key Golgi QC factor that detects and degrades orphaned membrane proteins with short transmembrane domains, preventing their spread and preserving membrane composition. Building on this, the project aims to uncover components that cooperate with the Dsc complex, focusing on Rer1—a retrieval receptor returning orphaned proteins to the ER. Combined loss of Dsc and Rer1 leads to Golgi QC failure, disrupted organelles, and membrane stress, triggering formation of multilamellar Golgi-derived compartments (GDCs) that activate Ypk1 signaling. This project will explore how Dsc and Rer1 maintain Golgi function, how GDCs form, and how Ypk1 mitigates stress. Using S. cerevisiae, the study integrates genetics, proteomics, and cryo-electron tomography to uncover a multilayered QC network at the Golgi. The findings will shed light on organelle integrity and proteostasis, key to understanding cellular health.