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IDOL Stimulates Clathrin-Independent Endocytosis and Multivesicular Body-Mediated Lysosomal Degradation of the Low-Density Lipoprotein Receptor
Open accessAbstract
The low-density lipoprotein receptor (LDLR) is a critical determinant of plasma cholesterol levels that internalizes lipoprotein cargo via clathrin-mediated endocytosis. Here, we show that the E3 ubiquitin ligase IDOL stimulates a previously unrecognized, clathrin-independent pathway for LDLR internalization. Real-time single-particle tracking and electron microscopy reveal that IDOL is recruited to the plasma membrane by LDLR, promotes LDLR internalization in the absence of clathrin or caveolae, and facilitates LDLR degradation by shuttling it into the multivesicular body (MVB) protein-sorting pathway. The IDOL-dependent degradation pathway is distinct from that mediated by PCSK9 as only IDOL employs ESCRT (endosomal-sorting complex required for transport) complexes to recognize and traffic LDLR to lysosomes. Small interfering RNA (siRNA)-mediated knockdown of ESCRT-0 (HGS) or ESCRT-I (TSG101) components prevents IDOL-mediated LDLR degradation. We further show that USP8 acts downstream of IDOL to deubiquitinate LDLR and that USP8 is required for LDLR entry into the MVB pathway. These results provide key mechanistic insights into an evolutionarily conserved pathway for the control of lipoprotein receptor expression and cellular lipid uptake.
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Scotti et al. reported findings similar to those reported here.
“While completing our study, Scotti et al. ( 56 ) reported fi ndings similar to those reported here.”
From The LXR-IDOL axis defines a clathrin-, caveolae-, and dynamin-independent endocytic route for LDLR internalization and lysosomal degradation (2013) · cites this paper as [56]
Both studies demonstrate that IDOL-stimulated internalization of the LDLR is clathrin-, caveolae-, and dynamin-independent, and identify the ESCRT system and associated DUB USP8 as important determinants for sorting ubiquitylated LDLR to MVBs.
“Both studies, using different methodologies, demonstrate that IDOL-stimulated internalization of the LDLR is clathrin-, caveolae-, and dynamin-independent, and identify the ESCRT system and associated DUB USP8 as important determinants for sorting ubiquitylated LDLR to MVBs.”
From The LXR-IDOL axis defines a clathrin-, caveolae-, and dynamin-independent endocytic route for LDLR internalization and lysosomal degradation (2013) · cites this paper as [56]
IDOL is implicated in lysosomal targeting and degradation of LDLR.
“the E3 ligase IDOL, which has also been implicated in lysosomal targeting and degradation of the LDLR (28,33,34).”
From A MARCH6 and IDOL E3 Ubiquitin Ligase Circuit Uncouples Cholesterol Synthesis from Lipoprotein Uptake in Hepatocytes (2016) · cites this paper as [33]
Citations
Cites
A Receptor-Mediated Pathway for Cholesterol Homeostasis
Brown, M. S., & Goldstein, J. L. (1986) · Science · doi:10.1126/science.3513311 · Cited by 5,703
Brown, M. S., & Goldstein, J. L. (1997) · Cell · doi:10.1016/s0092-8674(00)80213-5 · Cited by 3,834
Dynasore, a Cell-Permeable Inhibitor of Dynamin
Macia, E., Ehrlich, M., Massol, R., Boucrot, E., Brunner, C., & Kirchhausen, T. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.04.002 · Cited by 1,958
SINGLE-PARTICLE TRACKING:Applications to Membrane Dynamics
Saxton, M. J., & Jacobson, K. (1997) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.26.1.373 · Cited by 1,810
Feature point tracking and trajectory analysis for video imaging in cell biology
Sbalzarini, I. F., & Koumoutsakos, P. (2005) · Journal of Structural Biology · doi:10.1016/j.jsb.2005.06.002 · Cited by 1,403
The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins
Raiborg, C., & Stenmark, H. (2009) · Nature · doi:10.1038/nature07961 · Cited by 1,359
Regulation of Membrane Protein Transport by Ubiquitin and Ubiquitin-Binding Proteins
Hicke, L., & Dunn, R. (2003) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.19.110701.154617 · Cited by 1,131
LXR Regulates Cholesterol Uptake Through Idol-Dependent Ubiquitination of the LDL Receptor
Zelcer, N., Hong, C., Boyadjian, R., & Tontonoz, P. (2009) · Science · doi:10.1126/science.1168974 · Cited by 848
Self-citationThe emerging shape of the ESCRT machinery
Williams, R. L., & Urbé, S. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2162 · Cited by 779
Clathrin-independent endocytosis of ubiquitinated cargos
Sigismund, S., Woelk, T., Puri, C., Maspero, E., Tacchetti, C., Transidico, P., Di Fiore, P. P., & Polo, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409817102 · Cited by 739
Brown, M. S., & Goldstein, J. L. (1976) · Science · doi:10.1126/science.174194 · Cited by 725
Orlandi, P. A., & Fishman, P. H. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.4.905 · Cited by 721
Clathrin-mediated endocytosis in AP-2–depleted cells
Motley, A. M., Bright, N. A., Seaman, M. N. J., & Robinson, M. S. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200305145 · Cited by 709
Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and inlivers of parabiotic mice
Lagace, T. A., Curtis, D. E., Garuti, R., McNutt, M. C., Park, S. W., Prather, H. B., Anderson, N. N., Ho, Y. K., Hammer, R. E., & Horton, J. D. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29383 · Cited by 681
NARC-1/PCSK9 and Its Natural Mutants
Benjannet, S., Rhainds, D., Essalmani, R., Mayne, J., Wickham, L., Jin, W., Asselin, M.-C., Hamelin, J., Varret, M., Allard, D., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409699200 · Cited by 587
Hua, X., Yokoyama, C., Wu, J., Briggs, M. R., Brown, M. S., Goldstein, J. L., & Wang, X. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.24.11603 · Cited by 544
PCSK9: a convertase that coordinates LDL catabolism
Horton, J. D., Cohen, J. C., & Hobbs, H. H. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800091-jlr200 · Cited by 533
Rothberg, K. G., Ying, Y. S., Kamen, B. A., & Anderson, R. G. W. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.111.6.2931 · Cited by 532
ESCRT complexes and the biogenesis of multivesicular bodies
Hurley, J. H. (2008) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.12.002 · Cited by 497
Poirier, S., Mayer, G., Benjannet, S., Bergeron, E., Marcinkiewicz, J., Nassoury, N., Mayer, H., Nimpf, J., Prat, A., & Seidah, N. G. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708098200 · Cited by 477
Hrs regulates multivesicular body formation via ESCRT recruitment to endosomes
Bache, K. G., Brech, A., Mehlum, A., & Stenmark, H. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200302131 · Cited by 465
Maxwell, K. N., Fisher, E. A., & Breslow, J. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409736102 · Cited by 415
Deletion of Cavin/PTRF causes global loss of caveolae, dyslipidemia and glucose intolerance
Liu, L.-B., Brown, D., Mckee, M., LeBrasseur, N., Yang, D., Albrecht, K. H., Ravid, K., & Pilch, P. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.07.008 · Cited by 350
Self-citationStructural basis for selective recognition of ESCRT-III by the AAA ATPase Vps4
Obita, T., Saksena, S., Ghazi-Tabatabai, S., Gill, D. J., Perišić, O., Emr, S. D., & Williams, R. L. (2007) · Nature · doi:10.1038/nature06171 · Cited by 320
The role of ubiquitylation in receptor endocytosis and endosomal sorting
Haglund, K., & Đikić, I. (2012) · Journal of Cell Science · doi:10.1242/jcs.091280 · Cited by 310
Molecular mechanisms of clathrin-independent endocytosis
Hansen, C. G., & Nichols, B. (2009) · Journal of Cell Science · doi:10.1242/jcs.033951 · Cited by 295
Human Immunodeficiency Virus Type 1 Entry into Macrophages Mediated by Macropinocytosis
Maréchal, V., Prévost, M., Petit, C., Perret, E., Heard, J., & Schwartz, O. (2001) · Journal of Virology · doi:10.1128/jvi.75.22.11166-11177.2001 · Cited by 290
STAM and Hrs Are Subunits of a Multivalent Ubiquitin-binding Complex on Early Endosomes
Bache, K. G., Raiborg, C., Mehlum, A., & Stenmark, H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210843200 · Cited by 286
Domain map of the LDL receptor: Sequence homology with the epidermal growth factor precursor
Russell, D. W., Schneider, W. J., Yamamoto, T., Luskey, K. L., Brown, M. S., & Goldstein, J. L. (1984) · Cell · doi:10.1016/0092-8674(84)90388-x · Cited by 282
Liu, L., & Pilch, P. F. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m707890200 · Cited by 272
Self-citationTolleshaug, H., Hobgood, K. K., Brown, M. S., & Goldstein, J. L. (1983) · Cell · doi:10.1016/0092-8674(83)90079-x · Cited by 262
Fast and reversible trapping of surface glycine receptors by gephyrin
Meier, J. C., Vannier, C., Sergé, A., Triller, A., & Choquet, D. (2001) · Nature Neuroscience · doi:10.1038/85099 · Cited by 257
Poirier, S., Mayer, G., Poupon, V., McPherson, P. S., Desjardins, R., Ly, K., Asselin, M.-C., Day, R., Duclos, F. J., Witmer, M., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.037085 · Cited by 254
The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR
Nassoury, N., Blasiole, D. A., Tebon Oler, A., Benjannet, S., Hamelin, J., Poupon, V., McPherson, P. S., Attie, A. D., Prat, A., & Seidah, N. G. (2007) · Traffic · doi:10.1111/j.1600-0854.2007.00562.x · Cited by 248
Selective Caveolin-1–dependent Endocytosis of Glycosphingolipids
Singh, R. D., Puri, V., Valiyaveettil, J. T., Marks, D. L., Bittman, R., & Pagano, R. E. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-12-0809 · Cited by 242
Row, P. E., Prior, I. A., McCullough, J., Clague, M. J., & Urbé, S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512615200 · Cited by 239
Local clustering of transferrin receptors promotes clathrin-coated pit initiation
Liu, A. P., Aguet, F., Danuser, G. M., & Schmid, S. L. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201008117 · Cited by 230
McCullough, J., Row, P. E., Lorenzo, Ó., Doherty, M. K., Beynon, R. J., Clague, M. J., & Urbé, S. (2006) · Current Biology · doi:10.1016/j.cub.2005.11.073 · Cited by 206
Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis
Qian, Y.-W., Schmidt, R. J., Zhang, Y., Chu, S., Lin, A., Wang, H., Wang, X., Beyer, T. P., Bensch, W. R., Li, W., et al. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m700071-jlr200 · Cited by 194
PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide
Shan, L., Pang, L., Zhang, R., Murgolo, N. J., Lan, H., & Hedrick, J. A. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.07.106 · Cited by 180
Slow axonal transport: stop and go traffic in the axon
Brown, A. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35040102 · Cited by 173
Bowers, K., Piper, S. C., Edeling, M. A., Gray, S. R., Owen, D. J., Lehner, P. J., & Luzio, J. P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m508632200 · Cited by 166
Imaging the lateral diffusion of membrane molecules with quantum dots
Bannai, H., Lévi, S., Schweizer, C., Dahan, M., & Triller, A. (2006) · Nature Protocols · doi:10.1038/nprot.2006.429 · Cited by 162
Row, P. E., Liu, H., Hayes, S., Welchman, R., Charalabous, P., Hofmann, K., Clague, M. J., Sanderson, C. M., & Urbé, S. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704009200 · Cited by 160
Lipid rafts are required for GLUT4 internalization in adipose cells
Ros-Baró, A., López‐Iglesias, C., Peiró, S., Bellido, D., Palacı́n, M., Antonio Zorzano, A., & Camps, M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211341698 · Cited by 154
Miller, K., Beardmore, J. M., Kanety, H., Schlessinger, J., & Hopkins, C. R. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.102.2.500 · Cited by 150
Chen, H., & Camilli, P. V. D. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409719102 · Cited by 149
Bonneau, S., Dahan, M., & Cohen, L. D. (2005) · IEEE Transactions on Image Processing · doi:10.1109/tip.2005.852794 · Cited by 146
Endosomal compartmentalization in three dimensions: Implications for membrane fusion
Murk, J., Humbel, B. M., Ziese, U., Griffith, J. M., Posthuma, G., Slot, J. W., Koster, A. J., Verkleij, A. J., Geuze, H. J., & Kleijmeer, M. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2232379100 · Cited by 145
Hong, C., Duit, S., Jalonen, P., Out, R., Scheer, L., Sorrentino, V., Boyadjian, R., Rodenburg, K. W., Foley, E., Korhonen, L., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.123729 · Cited by 142
Self-citationCalcium cages, acid baths and recycling receptors
Brown, M. S., Herz, J., & Goldstein, J. L. (1997) · Nature · doi:10.1038/41672 · Cited by 137
Dermaut, B., Norga, K., Kania, A., Verstreken, P., Pan, H., Zhou, Y., Callaerts, P., & Bellen, H. J. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200412001 · Cited by 136
Keyel, P. A., Mishra, S. K., Roth, R., Heuser, J. E., Watkins, S. C., & Traub, L. M. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-05-0421 · Cited by 134
Shaping development with ESCRTs
Rusten, T. E., Vaccari, T., & Stenmark, H. (2011) · Nature Cell Biology · doi:10.1038/ncb2381 · Cited by 129
Differential functions of Hrs and ESCRT proteins in endocytic membrane trafficking
Raiborg, C., Malerød, L., Pedersen, N. M., & Stenmark, H. (2007) · Experimental Cell Research · doi:10.1016/j.yexcr.2007.10.014 · Cited by 126
Multiple Association States between Glycine Receptors and Gephyrin Identified by SPT Analysis
Ehrensperger, M.-V., Hanus, C., Vannier, C., Triller, A., & Dahan, M. (2007) · Biophysical Journal · doi:10.1529/biophysj.106.095596 · Cited by 122
Vesicle Formation at the Plasma Membrane and Trans-Golgi Network: The Same but Different
McNiven, M. A., & Thompson, H. M. (2006) · Science · doi:10.1126/science.1118133 · Cited by 122
The ESCRT machinery at a glance
Wollert, T., Yang, D., Ren, X., Lee, H. H., Im, Y. J., & Hurley, J. H. (2009) · Journal of Cell Science · doi:10.1242/jcs.029884 · Cited by 115
Lalanne, F., Lambert, G., Amar, M. J. A., Chétiveaux, M., Zaïr, Y., Jarnoux, A.-L., Ouguerram, K., Friburg, J., Seidah, N. G., Brewer, H. B., et al. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m400396-jlr200 · Cited by 104
Wang, Y., Huang, Y., Hobbs, H. H., & Cohen, J. C. (2012) · Journal of Lipid Research · doi:10.1194/jlr.m028563 · Cited by 104
Gephyrin Oligomerization Controls GlyR Mobility and Synaptic Clustering
Calamai, M., Specht, C. G., Heller, J. P., Alcor, D., Machado, P., Vannier, C., & Triller, A. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5711-08.2009 · Cited by 92
Self-citationThe IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL receptor
Zhang, L., Fairall, L., Goult, B. T., Calkin, A. C., Hong, C., Millard, C. J., Tontonoz, P., & Schwabe, J. W. R. (2011) · Genes & Development · doi:10.1101/gad.2056211 · Cited by 86
Self-citationTargeting of AMSH to Endosomes Is Required for Epidermal Growth Factor Receptor Degradation
Ma, Y. M., Boucrot, E., Villén, J., Affar, E. B., Gygi, S. P., Göttlinger, H. G., & Kirchhausen, T. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611635200 · Cited by 77
Scotti, E., Hong, C., Yoshinaga, Y., Tu, Y., Hu, Y., Zelcer, N., Boyadjian, R., de Jong, P. J., Young, S. G., Fong, L. G., et al. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.01469-10 · Cited by 77
Self-citationThi, H., Tselykh, T. V., Mäkelä, J., Ho, T. H., Olkkonen, V. M., Bornhauser, B. C., Korhonen, L., Zelcer, N., & Lindholm, D. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.341248 · Cited by 67
Calkin, A. C., Goult, B. T., Zhang, L., Fairall, L., Hong, C., Schwabe, J. W. R., & Tontonoz, P. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111589108 · Cited by 62
Self-citationAMSH, an ESCRT-III Associated Enzyme, Deubiquitinates Cargo on MVB/Late Endosomes
Kyuuma, M., Kikuchi, K., Kojima, K., Sugawara, Y., Sato, M., Mano, N., Goto, J., Takeshita, T., Yamamoto, A., Sugamura, K., et al. (2006) · Cell Structure and Function · doi:10.1247/csf.06023 · Cited by 60
Sorrentino, V., Scheer, L., Santos, A., Reits, E., Bleijlevens, B., & Zelcer, N. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.249557 · Cited by 53
Imaging LDL Receptor Oligomerization during Endocytosis Using a Co-internalization Assay
Zou, P., & Ting, A. Y. (2010) · ACS Chemical Biology · doi:10.1021/cb100361k · Cited by 26
Self-citationIshibashi, M., Masson, D., Westerterp, M., Wang, N., Sayers, S., Li, R., Welch, C. L., & Tall, A. R. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m006163 · Cited by 13
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Nair, J. K., Willoughby, J. L. S., Chan, A., Charisse, K., Alam, M. R., Wang, Q., Hoekstra, M., Kandasamy, P., Kel’in, A. V., Milstein, S., et al. (2014) · Journal of the American Chemical Society · doi:10.1021/ja505986a · Cited by 1,141
Self-citationLiver X receptors in lipid signalling and membrane homeostasis
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Traub, L. M., & Bonifacino, J. S. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016790 · Cited by 328
Minakaki, G., Menges, S., Kittel, A., Emmanouilidou, E., Schaeffner, I., Barkovits, K., Bergmann, A., Rockenstein, E., Adame, A., Marxreiter, F., et al. (2018) · Autophagy · doi:10.1080/15548627.2017.1395992 · Cited by 272
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Li, H., Yu, X.-H., Ou, X., Ouyang, X.-P., & Tang, C. (2021) · Progress in Lipid Research · doi:10.1016/j.plipres.2021.101109 · Cited by 237
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Gabitova, L., Gorin, A., & Astsaturov, I. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0122 · Cited by 115
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Paththinige, C., Sirisena, N., & Dissanayake, V. (2017) · Lipids in Health and Disease · doi:10.1186/s12944-017-0488-4 · Cited by 118
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Spencer, B. J., Emadi, S., Desplats, P., Eleuteri, S., Michael, S. A., Kosberg, K. A., Shen, J., Rockenstein, E. M., Patrick, C., Adame, A., et al. (2014) · Molecular Therapy · doi:10.1038/mt.2014.129 · Cited by 85
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Wijers, M., Kuivenhoven, J. A., & van de Sluis, B. (2015) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000157 · Cited by 55
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Škara, L., Huđek, A., Pezelj, I., Vrtarić, A., Sinčić, N., Krušlin, B., & Ulamec, M. (2021) · Cancers · doi:10.3390/cancers13184696 · Cited by 53
Bioactivity of Dietary Polyphenols: The Role in LDL-C Lowering
Sun, P., Zhao, L., Zhang, N., Zhou, J., Zhang, L., Wu, W., Ji, B., & Zhou, F. L. (2021) · Foods · doi:10.3390/foods10112666 · Cited by 52
Self-citationThe Deubiquitylase USP2 Regulates the LDLR Pathway by Counteracting the E3-Ubiquitin Ligase IDOL
Nelson, J. K., Sorrentino, V., Avagliano Trezza, R., Heride, C., Urbe, S., Distel, B., & Zelcer, N. (2016) · Circulation Research · doi:10.1161/circresaha.115.307298 · Cited by 51
Clathrin-mediated endocytosis is a candidate entry sorting mechanism for Bombyx mori cypovirus
Chen, F., Zhu, L., Zhang, Y., Kumar, D., Cao, G., Hu, X., Liang, Z., Kuang, S., Xue, R., & Gong, C. (2018) · Scientific Reports · doi:10.1038/s41598-018-25677-1 · Cited by 51
PCSK9 Promotes LDLR Degradation by Preventing SNX17-Mediated LDLR Recycling
Guan, Y., Liu, X., Yang, Z., Zhu, X., Liu, M., Du, M., Pan, X., & Wang, Y. (2025) · Circulation · doi:10.1161/circulationaha.124.072336 · Cited by 50
Spencer, B. J., Verma, I. M., Desplats, P., Friedmann‐Morvinski, D., Rockenstein, E. M., Adame, A., & Masliah, E. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.557439 · Cited by 50
Loregger, A., Cook, E. C. L., Nelson, J. K., Moeton, M., Sharpe, L. J., Engberg, S., Karimova, M., Lambert, G., Brown, A. J., & Zelcer, N. (2016) · Molecular and Cellular Biology · doi:10.1128/mcb.00890-15 · Cited by 48
Mbah, N. E., Overmeyer, J. H., & Maltese, W. A. (2016) · Cell Biology and Toxicology · doi:10.1007/s10565-016-9369-2 · Cited by 45
The hepatic WASH complex is required for efficient plasma LDL and HDL cholesterol clearance
Wijers, M., Zanoni, P., Liv, N., Vos, D. Y., Jäckstein, M. Y., Smit, M., Wilbrink, S., Wolters, J. C., van der Veen, Y. T., Huijkman, N., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.126462 · Cited by 44
Metabolic regulation through the endosomal system
Gilleron, J., Gerdes, J. M., & Zeigerer, A. (2019) · Traffic · doi:10.1111/tra.12670 · Cited by 42
Ubiquitin-mediated regulation of sterol homeostasis
van den Boomen, D. J. H., Volkmar, N., & Lehner, P. J. (2020) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2020.04.010 · Cited by 41
Naito, S., Makhov, P. B., Astsaturov, I. A., Golovine, K. V., Tulin, A. V., Kutikov, A., Uzzo, R. G., & Kolenko, V. M. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.77 · Cited by 39
Lochab, S., Pal, P., Kapoor, I., Kanaujiya, J. K., Sanyal, S., Behre, G., & Trivedi, A. K. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.018 · Cited by 35
Vos, D. Y., & van de Sluis, B. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101146 · Cited by 35
Targeting Liver X Receptors for the Treatment of Non-Alcoholic Fatty Liver Disease
Kim, H.-J., Park, C., & Kim, T. H. (2023) · Cells · doi:10.3390/cells12091292 · Cited by 34
Gao, J., Marosi, M., Choi, J., Achiro, J. M., Kim, S., Li, S., Otis, K., Martin, K. C., Portera-Cailliau, C., & Tontonoz, P. (2017) · eLife · doi:10.7554/elife.29178 · Cited by 30
Self-citationZhang, C.-P., Tian, Y., Zhang, M., Tuo, Q.-H., Chen, J.-X., & Liao, D.-F. (2016) · Medical Hypotheses · doi:10.1016/j.mehy.2015.11.010 · Cited by 28
IDOL regulates systemic energy balance through control of neuronal VLDLR expression
Lee, S. D., Priest, C., Bjursell, M., Gao, J., Arneson, D. V., Ahn, I. S., Diamante, G., van Veen, J. E., Massa, M. G., Calkin, A. C., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0127-7 · Cited by 26
Self-citationvan Loon, N. M., Lindholm, D., & Zelcer, N. (2019) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000593 · Cited by 25
SUMOylation of the ubiquitin ligase IDOL decreases LDL receptor levels and is reversed by SENP1
Wang, J.-Q., Lin, Z.-C., Li, L.-L., Zhang, S.-F., Li, W.-H., Liu, W., Song, B.-L., & Luo, J. (2021) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.015420 · Cited by 24
Nelson, J. K., Cook, E. C. L., Loregger, A., Hoeksema, M. A., Scheij, S. S., Kovačević, I., Hordijk, P. L., Ovaa, H., & Zelcer, N. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.698688 · Cited by 23
The promises of PCSK9 inhibition
Petrides, F., Shearston, K., Chatelais, M., Guilbaud, F., Meilhac, O., & Lambert, G. C. (2013) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328361f62d · Cited by 21
Starr, A. E., Lemieux, V., Noad, J., Moore, J. I., Dewpura, T., Raymond, A., Chrétien, M., Figeys, D., & Mayne, J. (2015) · FEBS Journal · doi:10.1111/febs.13309 · Cited by 21
Deubiquitylating enzymes in receptor endocytosis and trafficking
McCann, A. P., Scott, C. J., Schaeybroeck, S. V., & Burrows, J. F. (2016) · Biochemical Journal · doi:10.1042/bcj20160826 · Cited by 21
Do, H. T., Bruelle, C., Tselykh, T., Jalonen, P., Korhonen, L., & Lindholm, D. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.500967 · Cited by 20
Lysosome-targeting chimeras enable targeted protein degradation
Li, B., Li, Y., Zhang, J. J., Badama, S., Zhao, X., Wang, L., Zhang, T. W., Wang, X., Yi, X., Ding, G., et al. (2026) · Cell chemical biology · doi:10.1016/j.chembiol.2026.01.008 · Cited by 18
Vos, D. Y., Wijers, M., Smit, M., Huijkman, N., Kloosterhuis, N. J., Wolters, J. C., Tissink, J. J., Pronk, A. C. M., Kooijman, S., Rensen, P. C. N., et al. (2023) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.122.318169 · Cited by 16
Liao, G., Liu, W., Dai, Y., Shi, X., Liu, Y., Li, D., & Xu, T. (2023) · iScience · doi:10.1016/j.isci.2023.108337 · Cited by 16
Distribution of the LDL receptor within clathrin-coated pits and caveolae in rat and human liver
Ivaturi, S., Wooten, C. J., Nguyen, M. D., Ness, G. C., & Lopez, D. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.02.019 · Cited by 16
Martinelli, L., Adamopoulos, A., Johansson, P., Wan, P. T., Gunnarsson, J., Guo, H., Boyd, H., Zelcer, N., & Sixma, T. K. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.014349 · Cited by 14
Capitini, C., Bigi, A., Parenti, N., Emanuele, M., Bianchi, N., Cascella, R., Cecchi, C., Maggi, L., Annunziato, F., Pavone, F. S., et al. (2023) · iScience · doi:10.1016/j.isci.2023.106611 · Cited by 14
Self-citationMorales, S. V., Mahmood, A. A., Pollard, J., Mayne, J., Figeys, D., & Wiseman, P. W. (2023) · Biophysical Journal · doi:10.1016/j.bpj.2023.08.005 · Cited by 11
How active cholesterol coordinates cell cholesterol homeostasis: Test of a hypothesis
Lange, Y., & Steck, T. L. (2024) · Progress in Lipid Research · doi:10.1016/j.plipres.2024.101304 · Cited by 11
Khasa, R., Sharma, P., Vaidya, A., Vrati, S., & Kalia, M. (2020) · Microbial Pathogenesis · doi:10.1016/j.micpath.2020.104565 · Cited by 11
Aldworth, H., & Hooper, N. M. (2024) · Biochemical Society Transactions · doi:10.1042/bst20230918 · Cited by 11
Liang, C., Wang, X., Peng, K., Lai, P., Liu, Z., Ma, J., Chen, X., Liu, G., Zheng, M., Wang, Y., et al. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/1889632 · Cited by 8
Mlera, L., Collins-McMillen, D. K., Zeltzer, S., Buehler, J., Moy, M. A., Zarrella, K., Caviness, K., Cicchini, L., Tafoya, D. J., & Goodrum, F. D. (2023) · Journal of Virology · doi:10.1128/jvi.00758-23 · Cited by 9
Foiling IDOL to Help Control Cholesterol
Brown, A. J., & Hsieh, J. (2016) · Circulation Research · doi:10.1161/circresaha.116.308191 · Cited by 9
Hydrogen sulfide accumulates LDL receptor precursor via downregulating PCSK9 in HepG2 cells
Huang, Y. C., Ning, K., Li, W., Lin, G., Hou, C., Wang, M.-J., & Zhu, Y. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00244.2019 · Cited by 8
Sun, J., Liu, H.-R., Zhang, W., Shi, J., Wu, Q., Xu, R., & Zhu, Y. (2025) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2025.12796 · Cited by 7
Gene Therapy for Hypercholesterolemia
Huff, M. W., Assini, J. M., & Hegele, R. A. (2014) · Circulation Research · doi:10.1161/circresaha.114.304800 · Cited by 6
Wang, W., Chen, X., Chen, J., Xu, M., Liu, Y., Yang, S., Zhao, W., & Tan, S. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102115 · Cited by 5
Li, Z., Li, J., Li, Z., Song, Y., Wang, Y., Wang, C., Yuan, L., Xiao, W., & Wang, J. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1012227 · Cited by 4
IDOL Deficiency Inhibits Cholesterol-Rich Diet–Induced Atherosclerosis in Rabbits
Koike, T., Koike, Y., Niimi, M., Guo, Y., Yang, D., Song, J. W., Xu, J., Tang, X., Ren, Z., Kong, X., et al. (2025) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.125.322417 · Cited by 3
As a matter of fat: Emerging roles of lipid‐sensitive E3 ubiquitin ligases
Gawden‐Bone, C. M., Lehner, P. J., & Volkmar, N. (2023) · BioEssays · doi:10.1002/bies.202300139 · Cited by 2
Ugolotti, M., Papotti, B., Trentini, A., Mola, G., Cervellati, C., Adorni, M. P., & Zimetti, F. (2025) · Current Pharmaceutical Design · doi:10.2174/0113816128411158250909151734 · Cited by 2
Endocytosis of Cargo Proteins: LDL
Traub, L. M. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-394447-4.30024-4 · Cited by 1
Clathrin-independent endocytosis – role in disease processes and pharmaceutical aspects
Konopska, B., Gołąb, K., & Gburek, J. (2015) · Postępy Higieny i Medycyny Doświadczalnej · doi:10.5604/17322693.1160614
Regulation of cholesterol metabolism: An IDOL-dependent pathway to degrade the LDL-receptor
Sorrentino, V. (2014) · UvA-DARE (University of Amsterdam)
Chahdi, A., Yousefi, K., Capcha, J. M. C., Irion, C. I., Lambert, G., Shehadeh, S. A., Dunkley, J. C., Lee, Y., Khan, A., Ramic, M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.11.06.372292
Lagadinou, M., Efthymiou, D., Sampsonas, F., Karidis, P., Marlafeka, I., Adamopoulou, E., Michailides, C., Bosgana, P., Παπαϊωάννου, Ο., Psarros, E., et al. (2026) · Cancers · doi:10.3390/cancers18030374
Yokoyama, K., Chiba, M., Takei, N., Suto, K., Ishio, T., Goto, H., Endo, T., Kadin, M. E., Maeda, M., Watanabe, M., et al. (2026) · Oncogene · doi:10.1038/s41388-026-03970-y
Metadata
- Authors
- Scotti, E., Calamai, M., Goulbourne, C. N., Zhang, L., Hong, C., Lin, R. R., Choi, J., Pilch, P. F., Fong, L. G., Zou, P., Ting, A. Y., Pavone, F. S., Young, S. G., & Tontonoz, P.
- Affiliations
- Howard Hughes Medical Institute (US)
- Neuroscience Institute (IT)
- University of California, Los Angeles (US)
- Boston University (US)
- Massachusetts Institute of Technology (US)
- European Laboratory for Non-Linear Spectroscopy (IT)
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2013-04-01
- Volume
- 33
- Issue
- 8
- Pages
- 1503-1514
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC3624246
- OpenAlex
- W2069385307
- Semantic Scholar
- e89e5dcf78188828f87abf3499aaa5916245e925
- Cited by
- 81
- References
- 70
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 3 · 2021: 4 · 2020: 6 · 2019: 8 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 12 · 2014: 11 · 2013: 7
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- U.S. Public Health Service (CJX1-443835-WS-29646)
- National Heart, Lung, and Blood Institute (P01HL090553, R01HL066088)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- idols, LDL receptor, clathrin-independent endocytosis, multivesicular bodies, lysosomal degradation, ESCRT complex, ESCRT-0, ESCRT-I, TSG101, USP8, deubiquitination, cholesterol homeostasis, lipoprotein uptake, caveolae, PCSK9
- MeSH terms
- Proprotein Convertase 9, Tsg101 Protein, Animals, Cell Line, Clathrin, DNA-Binding Proteins, Endocytosis, HeLa Cells, Humans, Lipoproteins, LDL, Lysosomes, Nuclear Proteins, Endopeptidases, Phosphoproteins, Receptors, LDL, Serine Endopeptidases, Transcription Factors, Cell Cycle Proteins, Guanine Nucleotide Exchange Factors, Protein Transport, RNA Interference, RNA, Small Interfering, Ubiquitin Thiolesterase, Proprotein Convertases, Ubiquitin-Protein Ligases, Mice, Ubiquitination, Endosomal Sorting Complexes Required for Transport, Hep G2 Cells, Multivesicular Bodies, HEK293 Cells
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