Endospanins regulate a postinternalization step of the leptin receptor endocytic pathway

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Karin Séron - (Author)
  • Cyril Couturier - (Author)
  • Sandrine Belouzard - (Author)
  • Johan Bacart - (Author)
  • Didier Monté - (Author)
  • Laetitia Corset - (Author)
  • Olivier Bocquet - (Author)
  • Julie Dam - (Author)
  • Virginie Vauthier - (Author)
  • Cécile Lecoeur - (Author)
  • Bernard Bailleul - (Author)
  • Bernard Hoflack - , TUD Dresden University of Technology (Author)
  • Philippe Froguel - (Author)
  • Ralf Jockers - (Author)
  • Yves Rouillé - (Author)

Abstract

Endospanin-1 is a negative regulator of the cell surface expression of leptin receptor (OB-R), and endospanin-2 is a homologue of unknown function. We investigated the mechanism for endospanin-1 action in regulating OB-R cell surface expression. Here we show that endospanin-1 and -2 are small integral membrane proteins that localize in endosomes and the trans-Golgi network. Antibody uptake experiments showed that both endospanins are transported to the plasma membrane and then internalized into early endosomes but do not recycle back to the trans-Golgi network. Overexpression of endospanin-1 or endospanin-2 led to a decrease of OB-R cell surface expression, whereas shRNA-mediated depletion of each protein increased OB-R cell surface expression. This increased cell surface expression was not observed with OB-Ra mutants defective in endocytosis or with transferrin and EGF receptors. Endospanin-1 or endospanin-2 depletion did not change the internalization rate of OB-Ra but slowed down its lysosomal degradation. Thus, both endospanins are regulators of postinternalization membrane traffic of the endocytic pathway of OB-R.

Details

Original languageEnglish
Pages (from-to)17968-17981
Number of pages14
JournalJournal of Biological Chemistry
Volume286
Issue number20
Publication statusPublished - 20 May 2011
Peer-reviewedYes
Externally publishedYes

Keywords