RRC ID 46054
Author Dang H, Klokk TI, Schaheen B, McLaughlin BM, Thomas AJ, Durns TA, Bitler BG, Sandvig K, Fares H.
Title Derlin-dependent retrograde transport from endosomes to the Golgi apparatus.
Journal Traffic
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.
Volume 12(10)
Pages 1417-31
Published 2011-10-1
DOI 10.1111/j.1600-0854.2011.01243.x
PMID 21722281
PMC PMC4596261
MeSH Animals Blotting, Western Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / metabolism* Endocytosis / physiology Endosomes / metabolism* Golgi Apparatus / metabolism* HeLa Cells Humans Immunoprecipitation Macrophages / metabolism Macrophages / physiology Membrane Proteins / metabolism* Mice Protein Folding Protein Transport Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Sorting Nexins / metabolism Two-Hybrid System Techniques
IF 4.045
Times Cited 16
C.elegans tm847 tm3790 tm1320