title: Derlin-dependent retrograde transport from endosomes to the Golgi apparatus.
abstract: Cells have to maintain stable plasma membrane protein and lipid compositions under normal conditions and to remodel their plasma membranes in response to stimuli. This maintenance and remodeling require that integral membrane proteins at the plasma membrane that become misfolded, because of the relatively harsher extracellular milieu or carbohydrate and amino acid sequence changes, are degraded. We had previously shown that Derlin proteins, required for quality control mechanisms in the endoplasmic reticulum, also localize to endosomes and function in the degradation of misfolded integral membrane proteins at the plasma membrane. In this study, we show that Derlin proteins physically associate with sorting nexins that function in retrograde membrane transport from endosomes to the Golgi apparatus. Using genetic studies in Caenorhabditis elegans and ricin pulse-chase analyses in murine RAW264.7 macrophages, we show that the Derlin-sorting nexin interaction is physiologically relevant. Our studies suggest that at least some integral membrane proteins that are misfolded at the plasma membrane are retrogradely transported to the Golgi apparatus and ultimately to the endoplasmic reticulum for degradation via resident quality control mechanisms.
authors: Department of Molecular and Cellular Biology, Life Sciences South Room 531, University of Arizona, Tucson, AZ 85721, USA.
authors: Hope
authors: H
authors: Dang
authors: Tove I
authors: TI
authors: Klokk
authors: Basil
authors: B
authors: Schaheen
authors: Brooke M
authors: BM
authors: McLaughlin
authors: Anthony J
authors: AJ
authors: Thomas
authors: Tyler A
authors: TA
authors: Durns
authors: Benjamin G
authors: BG
authors: Bitler
authors: Kirsten
authors: K
authors: Sandvig
authors: Hanna
authors: H
authors: Fares
mesh_terms: D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008264:Macrophages / Q000378:metabolism / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D017510:Protein Folding; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D058305:Sorting Nexins / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D029742:Caenorhabditis elegans Proteins; C487709:DERL1 protein, human; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D058305:Sorting Nexins; C530424:derlin-1 protein, mouse