Regulation and Function of E3 ligases in the Golgi apparatus

The Golgi apparatus is an essential organelle that serves as the central hub of intracellular protein sorting and trafficking. It is a highly dynamic structure composed of tethered stacks of membranes required to cope with membrane and protein influx and transport to support cellular trafficking. Considering its central role in the secretory pathway, alternations in the structure and function of the Golgi are involved in many human diseases such as neurodegenerative diseases, ischemic stroke, cardiovascular diseases, pulmonary arterial hypertension, infectious diseases and cancer.

Inspired by other studies demonstrating that ubiquitination of Golgi resident proteins play a role in Golgi function and homeostasis, our research focuses on the regulation and function of E3 ligases in the Golgi. Unlike the endoplasmic reticulum (ER) that is well studied and more than 30 E3 ligases were reported to be located in the ER, very few E3 ligases are exclusively located in the Golgi and not much is known about their regulation and their substrates scope. To this end, we chose to investigate Golgi-resident E3 ligases, verify their Golgi localization and study their regulation by Golgi stressors. In addition, we generated CRISPR/Cas9 knock out (KO) cells for these E3 ligases and examine whether Golgi structures are altered in cells. Future proteomics approaches will be used to elucidate the substrates of these E3 ligases. As alterations in Golgi function are associated with various human diseases, our research may shed light on the molecular mechanism of Golgi regulation with therapeutic implications.