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
|
WOS Category
|
CELL BIOLOGY
|
Resource |
C.elegans |
tm847
tm3790
tm1320 |