Glycan regulation of ER-associated degradation through compartmentalization

The internal environment of the eukaryotic cell is divided by membranes into various organelles, containing diverse functional subcompartments, which allow complex cellular life. The quality control of newly made secretory proteins relies on the ability of the endoplasmic reticulum (ER) to segregate and compartmentalize molecules at different folding states. These folding states are communicated by N-glycans present on most secretory proteins. In ER-associated degradation (ERAD), protein molecules that have been identified as terminally misfolded are sent for degradation at the cytosolic proteasomes after being dislocated from the ER to the cytosol. This review will focus on how misfolded glycoprotein molecules are segregated from their properly folded counterparts and targeted to ERAD. The pathway involves compartmentalization, which is intimately linked to differential N-glycan processing. Recent data suggests that these processes are very dynamic, and include transient assembly of ERAD machinery complexes. (C) 2014 Elsevier Ltd. All rights reserved.