The LXR-IDOL axis defines a clathrin-, caveolae-, and dynamin-independent endocytic route for LDLR internalization and lysosomal degradation

Goldstein, 2009, The LDL receptor, Arterioscler. Thromb. Vasc. Biol., 29, 431, 10.1161/ATVBAHA.108.179564 Brown, 1986, A receptor-mediated pathway for cholesterol homeostasis, Science., 232, 34, 10.1126/science.3513311 Garcia, 2001, Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein, Science., 292, 1394, 10.1126/science.1060458 Keyel, 2006, A single common portal for clathrin-mediated endocytosis of distinct cargo governed by cargo-selective adaptors, Mol. Biol. Cell., 17, 4300, 10.1091/mbc.e06-05-0421 Chen, 1990, NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor, J. Biol. Chem., 265, 3116, 10.1016/S0021-9258(19)39742-X He, 2002, ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2, J. Biol. Chem., 277, 44044, 10.1074/jbc.M208539200 Morris, 2001, Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2, Traffic., 2, 111, 10.1034/j.1600-0854.2001.020206.x Michaely, 2007, Identification of a VLDL-induced, FDNPVY-independent internalization mechanism for the LDLR, EMBO J., 26, 3273, 10.1038/sj.emboj.7601769 McMahon, 2011, Molecular mechanism and physiological functions of clathrin-mediated endocytosis, Nat. Rev. Mol. Cell Biol., 12, 517, 10.1038/nrm3151 Motley, 2003, Clathrin-mediated endocytosis in AP-2-depleted cells, J. Cell Biol., 162, 909, 10.1083/jcb.200305145 Sigismund, 2008, Clathrin-mediated internalization is essential for sustained EGFR signaling but dispensable for degradation, Dev. Cell., 15, 209, 10.1016/j.devcel.2008.06.012 Howes, 2010, Molecules, mechanisms, and cellular roles of clathrin-independent endocytosis, Curr. Opin. Cell Biol., 22, 519, 10.1016/j.ceb.2010.04.001 Sigismund, 2012, Endocytosis and signaling: cell logistics shape the eukaryotic cell plan, Physiol. Rev., 92, 273, 10.1152/physrev.00005.2011 MacGurn, 2012, Ubiquitin and membrane protein turnover: from cradle to grave, Annu. Rev. Biochem., 81, 231, 10.1146/annurev-biochem-060210-093619 Goldstein, 2006, Protein sensors for membrane sterols, Cell., 124, 35, 10.1016/j.cell.2005.12.022 Horton, 2002, SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver, J. Clin. Invest., 109, 1125, 10.1172/JCI0215593 Davis, 1986, The J.D. mutation in familial hypercholesterolemia: amino acid substitution in cytoplasmic domain impedes internalization of LDL receptors, Cell., 45, 15, 10.1016/0092-8674(86)90533-7 Hobbs, 1990, The LDL receptor locus in familial hypercholesterolemia: mutational analysis of a membrane protein, Annu. Rev. Genet., 24, 133, 10.1146/annurev.ge.24.120190.001025 Zelcer, 2006, Liver X receptors as integrators of metabolic and inflammatory signaling, J. Clin. Invest., 116, 607, 10.1172/JCI27883 Janowski, 1996, An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha, Nature., 383, 728, 10.1038/383728a0 Zelcer, 2009, LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor, Science., 325, 100, 10.1126/science.1168974 Sorrentino, 2011, Distinct functional domains contribute to degradation of the low density lipoprotein receptor (LDLR) by the E3 ubiquitin ligase inducible degrader of the LDLR (IDOL), J. Biol. Chem., 286, 30190, 10.1074/jbc.M111.249557 Sorrentino, 2012, Post-transcriptional regulation of lipoprotein receptors by the E3-ubiquitin ligase inducible degrader of the low-density lipoprotein receptor, Curr. Opin. Lipidol., 23, 213, 10.1097/MOL.0b013e3283532947 Razani, 2001, Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities, J. Biol. Chem., 276, 38121, 10.1074/jbc.M105408200 Zhao, 2008, The epidermal growth factor homology domain of the LDL receptor drives lipoprotein release through an allosteric mechanism involving H190, H562, and H586, J. Biol. Chem., 283, 26528, 10.1074/jbc.M804624200 Bishop, 2000, ATPase-defective mammalian VPS4 localizes to aberrant endosomes and impairs cholesterol trafficking, Mol. Biol. Cell., 11, 227, 10.1091/mbc.11.1.227 Kazazic, 2009, Epsin 1 is involved in recruitment of ubiquitinated EGF receptors into clathrin-coated pits, Traffic., 10, 235, 10.1111/j.1600-0854.2008.00858.x Motazacker, 2012, Advances in genetics show the need for extending screening strategies for autosomal dominant hypercholesterolaemia, Eur. Heart J., 33, 1360, 10.1093/eurheartj/ehs010 Song, 1996, Co-purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains. Detergent-free purification of caveolae microdomains, J. Biol. Chem., 271, 9690, 10.1074/jbc.271.16.9690 Hong, 2010, The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2, J. Biol. Chem., 285, 19720, 10.1074/jbc.M110.123729 Wilund, 2002, Molecular mechanisms of autosomal recessive hypercholesterolemia, Hum. Mol. Genet., 11, 3019, 10.1093/hmg/11.24.3019 Maurer, 2006, The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH, J. Cell Sci., 119, 4235, 10.1242/jcs.03217 Eden, 2007, Adaptor protein disabled-2 modulates low density lipoprotein receptor synthesis in fibroblasts from patients with autosomal recessive hypercholesterolaemia, Hum. Mol. Genet., 16, 2751, 10.1093/hmg/ddm232 Hannigan, 2010, Epigenetic downregulation of human disabled homolog 2 switches TGF-beta from a tumor suppressor to a tumor promoter, J. Clin. Invest., 120, 2842, 10.1172/JCI36125 Mizushima, 2001, Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells, J. Cell Biol., 152, 657, 10.1083/jcb.152.4.657 Simons, 2000, Lipid rafts and signal transduction, Nat. Rev. Mol. Cell Biol., 1, 31, 10.1038/35036052 Subtil, 1999, Acute cholesterol depletion inhibits clathrin-coated pit budding, Proc. Natl. Acad. Sci. USA., 96, 6775, 10.1073/pnas.96.12.6775 Sigismund, 2005, Clathrin-independent endocytosis of ubiquitinated cargos, Proc. Natl. Acad. Sci. USA., 102, 2760, 10.1073/pnas.0409817102 Polo, 2002, A single motif responsible for ubiquitin recognition and monoubiquitination in endocytic proteins, Nature., 416, 451, 10.1038/416451a Wendland, 2002, Epsins: adaptors in endocytosis?, Nat. Rev. Mol. Cell Biol., 3, 971, 10.1038/nrm970 Ford, 2002, Curvature of clathrin-coated pits driven by epsin, Nature., 419, 361, 10.1038/nature01020 Raiborg, 2009, The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins, Nature., 458, 445, 10.1038/nature07961 Fujita, 2003, A dominant negative form of the AAA ATPase SKD1/VPS4 impairs membrane trafficking out of endosomal/lysosomal compartments: class E vps phenotype in mammalian cells, J. Cell Sci., 116, 401, 10.1242/jcs.00213 Marchese, 2003, The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4, Dev. Cell., 5, 709, 10.1016/S1534-5807(03)00321-6 Clague, 2006, Endocytosis: the DUB version, Trends Cell Biol., 16, 551, 10.1016/j.tcb.2006.09.002 Lafont, 2001, Raft-partitioning of the ubiquitin ligases Cbl and Nedd4 upon IgE-triggered cell signaling, Proc. Natl. Acad. Sci. USA., 98, 3180, 10.1073/pnas.051003498 Horvath, 2007, Epsin: inducing membrane curvature, Int. J. Biochem. Cell Biol., 39, 1765, 10.1016/j.biocel.2006.12.004 Chen, 2009, Embryonic arrest at midgestation and disruption of Notch signaling produced by the absence of both epsin 1 and epsin 2 in mice, Proc. Natl. Acad. Sci. USA., 106, 13838, 10.1073/pnas.0907008106 Pasula, 2012, Endothelial epsin deficiency decreases tumor growth by enhancing VEGF signaling, J. Clin. Invest., 122, 4424, 10.1172/JCI64537 Chen, 2008, Epsin 1 is a cargo-specific adaptor for the clathrin-mediated endocytosis of the influenza virus, Proc. Natl. Acad. Sci. USA., 105, 11790, 10.1073/pnas.0803711105 Kang, 2013, Caenorhabditis elegans reveals a FxNPxY-independent low-density lipoprotein receptor internalization mechanism mediated by epsin1., Mol. Biol. Cell., 24, 308, 10.1091/mbc.e12-02-0163 Mizuno, 2005, Regulation of epidermal growth factor receptor down-regulation by UBPY-mediated deubiquitination at endosomes, Mol. Biol. Cell., 16, 5163, 10.1091/mbc.e05-06-0560 de Bie, 2011, Ubiquitination of E3 ligases: self-regulation of the ubiquitin system via proteolytic and non-proteolytic mechanisms, Cell Death Differ., 18, 1393, 10.1038/cdd.2011.16 Scotti, 2011, Targeted disruption of the idol gene alters cellular regulation of the low-density lipoprotein receptor by sterols and liver x receptor agonists, Mol. Cell. Biol., 31, 1885, 10.1128/MCB.01469-10 Wang, 2012, Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR, J. Lipid Res., 53, 1932, 10.1194/jlr.M028563 Scotti, 2013, IDOL stimulates clathrin-independent endocytosis and multivesicular body-mediated lysosomal degradation of the low-density lipoprotein receptor, Mol. Cell. Biol., 33, 1503, 10.1128/MCB.01716-12