title: The retrotranslocation protein Derlin-1 binds peptide:N-glycanase to the endoplasmic reticulum.
abstract: The deglycosylating enzyme, peptide:N-glycanase, acts on misfolded N-linked glycoproteins dislocated from the endoplasmic reticulum (ER) to the cytosol. Deglycosylation has been demonstrated to occur at the ER membrane and in the cytosol. However, the mechanism of PNGase association with the ER membrane was unclear, because PNGase lacked the necessary signal to facilitate its incorporation in the ER membrane, nor was it known to bind to an integral ER protein. Using HeLa cells, we have identified a membrane protein that associates with PNGase, thereby bringing it in close proximity to the ER and providing accessibility to dislocating glycoproteins. This protein, Derlin-1, has recently been shown to mediate retrotranslocation of misfolded glycoproteins. In this study we demonstrate that Derlin-1 interacts with the N-terminal domain of PNGase via its cytosolic C-terminus. Moreover, we find PNGase distributed in two populations; ER-associated and free in the cytosol, which suggests the deglycosylation process can proceed at either site depending on the glycoprotein substrate.
authors.affiliation: Department of Biochemistry and Cell Biology and The Institute for Cell and Developmental Biology, State University of New York-Stony Brook, Stony Brook, NY 11794, USA.
authors.forename: Samiksha
authors.initials: S
authors.lastname: Katiyar
authors.forename: Shivanjali
authors.initials: S
authors.lastname: Joshi
authors.forename: William J
authors.initials: WJ
authors.lastname: Lennarz
mesh_terms: D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006031:Glycosylation; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000378:metabolism*; D021381:Protein Transport
chemical_list: C487709:DERL1 protein, human; D008565:Membrane Proteins; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase