title: Glycan regulation of ER-associated degradation through compartmentalization.
abstract: 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.
authors.affiliation: Department of Cell Research and Immunology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Benyair
authors.affiliation: Department of Cell Research and Immunology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Navit
authors.initials: N
authors.lastname: Ogen-Shtern
authors.affiliation: Department of Cell Research and Immunology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: gerardo@post.tau.ac.il.
authors.forename: Gerardo Z
authors.initials: GZ
authors.lastname: Lederkremer
mesh_terms: D002451:Cell Compartmentation; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D060746:Endoplasmic Reticulum-Associated Degradation; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011134:Polysaccharides / Q000378:metabolism*; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport
chemical_list: D006023:Glycoproteins; D011134:Polysaccharides
keywords: Calnexin; ER quality control; ERAD; ERQC; Mannosidase; N-glycosylation