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| Subject Categories: Membranes & Transport |
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| The EMBO Journal
(2005) 24, 2851–2861, doi:10.1038/sj.emboj.7600756 Published online 28 July 2005 |
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| Sorting nexin 17 facilitates LRP recycling in the early endosome |
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| Peter van Kerkhof1, 2, 3, 4, Jiyeon Lee1, 2, 4, Lynn McCormick1, 2, Elena Tetrault1, 2, Wenyan Lu1, 2, Marissa Schoenfish1, 2, Viola Oorschot3, Ger J Strous3, Judith Klumperman3 and Guojun Bu1, 2 |
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1 Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA 2 Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO, USA 3 Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, Utrecht, the Netherlands To whom correspondence should be addressed Guojun Bu, Department of Pediatrics, Washington University School of Medicine, CB 8208, 660 South Euclid Ave, St Louis, MO 63110, USA. Tel.: +1 314 286 2860; Fax: +1 314 286 2894; E-mail: bu@wustl.edu 4 These authors contributed equally to this work Received 10 February 2005; Accepted 5 July 2005; Published online 28 July 2005. |
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| Abstract |
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| 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. |
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| Keywords: endosome, LRP, recycling, sorting, sorting nexin 17 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHThe EMBO Journal Article (15 Aug 2002) The EMBO Journal Article (01 Nov 2002) SNX3 regulates endosomal function through its PX-domain-mediated interaction with PtdIns(3)P Nature Cell Biology Article (01 Jul 2001) |
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