Yos9, a control protein for misfolded glycosylated and non-glycosylated proteins in ERAD

The endoplasmic reticulum (ER) is responsible for folding and delivery of secretory proteins to their site of action. One major modification proteins undergo in this organelle is N-glycosylation. Proteins that cannot fold properly will be directed to a process known as endoplasmic reticulum associated degradation (ERAD). Processing of N-glycans generates a signal for ERAD. The lectin Yos9 recognizes the N-glycan signal of misfolded proteins and acts as a gatekeeper for the delivery of these substrates to the cytoplasm for degradation. Presence of Yos9 accelerates degradation of the glycosylated model ERAD substrate CPY∗. Here we show that Yos9 has also a control function in degradation of the unglycosylated ERAD substrate CPY∗0000. It decelerates its degradation rate.

► Non-glycosylated model substrate CPY∗0000 is an ERAD-L substrate. ► The lectin Yos9 retains misfolded CPY∗0000 prior its delivery to the ERAD machinery. ► Yos9 plays a tuning roll in delivering glycosylated and unglycosylated misfolded proteins to ERAD.