CURIE · C53 and Ufmylation Regulation In Endoplasmic Reticulum-Autophagy (ER-phagy)
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-05-01 → 2023-04-30
- EU contribution
- €186,167
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
C53 and Ufmylation Regulation In Endoplasmic Reticulum-Autophagy (ER-phagy)
Persistent cellular stress impairs cell fitness and lifespan. When stress happens, protein aggregates will be formed, these could be cleared by the essential and fundamental cellular protein quality control pathway called autophagy. Defects in autophagy are linked to diverse diseases in humans and makes plants susceptible to stress. Endoplasmic reticulum (ER) has a central role for protein biosynthesis, it works together with ribosomes to synthesize, fold and modify lipid and transmembrane proteins. When ER stress happens, cell will initiate an ER-specific autophagic pathway celled “ER-phagy” to remove the damaged ER and maintain a healthy proteome. When ribosomes collide on the ER, another quality control mechanism will be triggered called “UFMylation”, this modification on certain ribosome protein will cooperates with ER-phagy to get rid of incompletely synthesized proteins at the ER-membrane. The host lab has discovered C53 protein as a conserved ER-phagy receptor from plants to humans. It forms a complex with UFMylation pathway E3 ligase and mediate the UFMylation of ribosome protein, meanwhile bind to autophagy receptor protein ATG8 and mediate ER-phagy. In this project, we dissect how UFMylation regulates C53-mediated ER-phagy, and what is the molecular switch mechanism that regulate the C53 function in normal conditions and under ER-stress. The project has achieved most of its objectives and milestones for the period, with relatively minor deviations. By the end of this action, together with my colleague, we structurally and genetically characterized C53-ATG8 and C53-UFM1 interaction. Apart from this, using proteomics, I determined the ufmylome in model plant Arabidopsis and established the pipeline for identifying ufmylation substrates in plants. The research carried on during this action expanded our current understanding of a novel ER quality control pathway in plants and our knowledge of ufmylation in plants.
Data: CORDIS, © European Union
Project objective
Autophagy is a highly selective cellular quality control pathway. Selective removal of autophagic cargo are mediated by cargo receptors that contain cargo binding domains and ATG8 interacting motifs to bridge the cargo with autophagosomes. Although cargo receptors are the key players linking autophagy to cellular quality control, most of them are still waiting to be uncovered in plants. Identification and characterization of novel cargo receptors will pave the way for future translational studies that aim to enhance stress tolerance in crop species.The host lab recently identified an Endoplasmic reticulum (ER) autophagy receptor C53, that interacts with ATG8 via non-canonical shuffled ATG8 interacting motif. Besides, C53 is regulated by an enigmatic posttranslational modification called ufmylation through binding to another ubiquitin-like protein UFM1. Interestingly, ATG8-UFM1 interaction is mutually exclusive. However, the structural basis of C53-ATG8 or C53-UFM1 interaction are currently unknown. Also, the physiological roles of ufmylation and the ufmylated protein substrates have not been studied in plants.In this proposal, I aim to structurally and genetically characterize C53-ATG8 and C53-UFM1 interaction. In parallel, using proteomics, I will determine the ufmylome, i.e., ufmylated protein catalogue in plants for the first time. Finally, I will move beyond model species Arabidopsis and establish autophagy and ufmylation studies in rice. Altogether, my studies will further our understanding of a novel ER quality control pathway in model plant species and beyond.I will work at the Gregor Mendel Institute (GMI), Vienna BioCenter (VBC) in the lab of Yasin Dagdas. VBC is one of the largest life sciences hubs in Europe. It has a dynamic postdoc community, with structured training programs to prepare postdocs for independent careers. The cutting-edge research concepts, resources, and soft-skill training that I will gain will help me to establish my own lab.
Original text from CORDIS.
Participants
- GREGOR MENDEL INSTITUT FUR MOLEKULARE PFLANZENBIOLOGIE GMBH · WIENCoordinatorAustria
Links
- View on CORDIS
- DOI: 10.3030/101028611
- https://www.oeaw.ac.at/gmi/research/research-groups/yasin-dagdas
Data: CORDIS, © European Union