title: Protein dislocation from the ER.
abstract: Protein folding within the endoplasmic reticulum (ER) of eukaryotic cells is erroneous and often results in the formation of terminally malfolded species. A quality control system retards such molecules in the ER and eventually initiates their dislocation into the cytosol for proteolysis by 26S proteasomes. This process is termed ER associated protein degradation (ERAD). The spatial separation of ER based quality control and cytosolic proteolysis poses the need for a machinery that promotes the extraction of substrates from the ER. Due to the heterogeneous nature of the client proteins this transport system displays several unique features. Selective recognition of ERAD substrates does not involve transferable transport signals in the primary sequence and thus must follow other principles than established for proteins designated for the import into organelles. Moreover, an ER dislocation system must be capable to ship polypeptides, which may be at least partly folded and are in most cases covalently modified with bulky and hydrophilic glycans, through a membrane without disrupting the integrity of the ER. In this review we present current ideas on the highly dynamic and flexible nature of the dislocation apparatus and speculate on the mechanism that removes aberrant polypeptides from the ER in the course of ERAD. This article is part of a Special Issue entitled Protein translocation across or insertion into membranes.
authors.affiliation: Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Bagola
authors.forename: Martin
authors.initials: M
authors.lastname: Mehnert
authors.forename: Ernst
authors.initials: E
authors.lastname: Jarosch
authors.forename: Thomas
authors.initials: T
authors.lastname: Sommer
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D021381:Protein Transport