title: Endospanins regulate a postinternalization step of the leptin receptor endocytic pathway.
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.
authors: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8199, 59021 Lille, France.
authors: Karin
authors: K
authors: Séron
authors: Cyril
authors: C
authors: Couturier
authors: Sandrine
authors: S
authors: Belouzard
authors: Johan
authors: J
authors: Bacart
authors: Didier
authors: D
authors: Monté
authors: Laetitia
authors: L
authors: Corset
authors: Olivier
authors: O
authors: Bocquet
authors: Julie
authors: J
authors: Dam
authors: Virginie
authors: V
authors: Vauthier
authors: Cécile
authors: C
authors: Lecœur
authors: Bernard
authors: B
authors: Bailleul
authors: Bernard
authors: B
authors: Hoflack
authors: Philippe
authors: P
authors: Froguel
authors: Ralf
authors: R
authors: Jockers
authors: Yves
authors: Y
authors: Rouillé
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism*; D021601:trans-Golgi Network / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C107590:LEPROT protein, human; D054411:Receptors, Leptin