Derlin-dependent retrograde transport from endosomes to the golgi apparatus

Hope Dang, Tove I. Klokk, Basil Schaheen, Brooke M. McLaughlin, Anthony J. Thomas, Tyler A. Durns, Benjamin G. Bitler, Kirsten Sandvig, Hanna Fares

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1417-1431
Number of pages15
JournalTraffic
Volume12
Issue number10
DOIs
StatePublished - Oct 2011

Keywords

  • Caenorhabditis elegans
  • Derlin
  • ERAD
  • Endocytosis
  • Misfolded proteins
  • Retromer
  • Ricin
  • Sorting nexin

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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