Mannosidase complexes involved in glycoprotein degradation

In all eukaryotic cells, the endoplasmic reticulum (ER) has a central role in protein biosynthesis and maturation. Folding of newly synthesized secretory and membrane proteins takes place in the lumen of the ER. Properly folded and assembled proteins exit the ER and continue their journey in the secretory pathway. However, protein folding is error-prone and the accumulation of misfolded or surplus proteins endangers the cellular homeostasis and subsequently the survival of organisms especially under adverse environmental conditions. Consequently, cells have established sophisticated quality control processes that ensure the export of biologically active proteins and the elimination of non-native ones. These quality control processes involve proteins that sense folding-defective proteins and target them for destruction by a precisely controlled protein breakdown process known as ER-associated degradation (ERAD). The degradation of folding-defective glycoproteins is initiated in the lumen of the ER and the specific proteins that recognize the misfolded glycoproteins and determine their fate are unknown. We hypothesize that protein complexes consisting of alpha-mannosidases and thioredoxin-fold containing proteins are key factors in this process. The role of these complexes will be investigated using genetic, biochemical and cell biology approaches. The project will help to better understand protein quality control mechanisms in plants, which, in the long run, will lead to new strategies to improve plant fitness under constantly changing environmental conditions.