Sorting nexin 17 facilitates LRP recycling in the early endosome

Peter Van Kerkhof, Jiyeon Lee, Lynn McCormick, Elena Tetrault, Wenyan Lu, Marissa Schoenfish, Viola Oorschot, Ger J. Strous, Judith Klumperman, Guojun Bu

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

The low-density lipoprotein (LDL) receptor-related protein (LRP) is a multiligand endocytic receptor and a member of the LDL receptor family. Here we show that sorting nexin 17 (Snx17) is part of the cellular sorting machinery that regulates cell surface levels of LRP by promoting its recycling. While the phox (PX) domain of Snx17 interacts with phosphatidylinositol-3-phosphate for membrane association, the FERM domain and the carboxyl-terminal region participate in LRP binding. Immunoelectron microscopy shows that the membrane-bound fraction of Snx17 is localized to the limiting membrane and recycling tubules of early endosomes. The NPxY motif, proximal to the plasma membrane in the LRP cytoplasmic tail, is identified as the Snx17-binding motif. Functional mutation of this motif did not interfere with LRP endocytosis, but decreased LRP recycling from endosomes, resulting in increased lysosomal degradation. Similar effects are found after knockdown of endogenous Snx17 expression by short interfering RNA. We conclude that Snx17 binds to a motif in the LRP tail distinct from the endocytosis signals and promotes LRP sorting to the recycling pathway in the early endosomes.

Original languageEnglish (US)
Pages (from-to)2851-2861
Number of pages11
JournalEMBO Journal
Volume24
Issue number16
DOIs
StatePublished - Aug 17 2005

Keywords

  • Endosome
  • LRP
  • Recycling
  • Sorting
  • Sorting nexin 17

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Sorting nexin 17 facilitates LRP recycling in the early endosome'. Together they form a unique fingerprint.

  • Cite this

    Van Kerkhof, P., Lee, J., McCormick, L., Tetrault, E., Lu, W., Schoenfish, M., Oorschot, V., Strous, G. J., Klumperman, J., & Bu, G. (2005). Sorting nexin 17 facilitates LRP recycling in the early endosome. EMBO Journal, 24(16), 2851-2861. https://doi.org/10.1038/sj.emboj.7600756