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J Biol Chem. 2003 Jun 6;278(23):21155-61. Epub 2003 Mar 25.

Enterophilin-1, a new partner of sorting nexin 1, decreases cell surface epidermal growth factor receptor.

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  • 1Institut Fédératif de Recherche Claude de Préval, IFR 30, Université Paul Sabatier, and Centre Hospitalo-Universitaire de Toulouse, INSERM Unité 563, Department of Lipoproteins and Lipid Mediators, Hôpital Purpan, F31059 Toulouse Cedex, France.

Abstract

We previously described enterophilin-1 (Ent-1), a new intestinal protein bearing an extended leucine zipper and a B30.2 domain. Ent-1 expression is associated with growth arrest and enterocyte differentiation. To investigate the importance of Ent-1 in the differentiation, we performed a yeast two-hybrid screening. We identified sorting nexin 1 (SNX1) as a novel partner of Ent-1 and confirmed the specificity of interaction by co-immunoprecipitation experiments in mammalian cells. SNX1 is associated with endosomal membranes and triggers the endosome-to-lysosome pathway of epidermal growth factor receptor (EGFR). We observe by immunofluorescence microscopy that Ent-1 and SNX1 are co-localized on vesicular and tubulovesicular structures, which are different from early endosome antigen 1-containing endosomes. By gel filtration chromatography, we show that Ent-1 and SNX1 co-eluted in macromolecular complexes containing part of EGFR. Furthermore, overexpressed Ent-1 decreases cell surface EGFR. Ent-1 and SNX1 co-overexpression strongly extends EGFR diminution, indicating a synergetic effect of both proteins on cell surface EGFR removal. Interestingly, the increase of endogenous Ent-1 expression correlates with the decrease of EGFR during spontaneous differentiation of Caco-2 cells. We thus propose a role of Ent-1 in the trafficking of EGFR to down-regulate intestinal mitogenic signals, highlighting the mechanisms of cell growth arrest associated with enterocytic differentiation.

PMID:
12657642
[PubMed - indexed for MEDLINE]
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