Protein folding is inherently error prone, especially in the endoplasmic reticulum (ER). Even
with an elaborate network of molecular chaperones and protein folding facilitators,
misfolding can occur quite frequently. To maintain protein homeostasis, eukaryotes have
evolved a series of protein quality-control checkpoints. When secretory pathway quality-
control pathways fail, stress response pathways, such as the unfolded protein response
(UPR), are induced. In addition, the ER, which is the initial hub of protein biogenesis in the …

Misfolded proteins of the secretory pathway are distinguished and degraded by cellular
mechanisms collectively called'quality control'. The three parts of this thesis work all
contribute to understanding the molecular mechanisms of protein quality control. The first
part is about the post-ER quality control that includes two different mechanisms, a direct
delivery pathway to the vacuole and turnover from the plasma Membrane. Pma1-10, a
mutant of plasma membrane H+-ATPase (Pma1), is a substrate that can be delivered to the …