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Ligands for Clathrin-Mediated Endocytosis Are Differentially Sorted into Distinct Populations of Early Endosomes
Abstract
Cells rely on the correct sorting of endocytic ligands and receptors for proper function. Early endosomes have been considered as the initial sorting station where cargos for degradation separate from those for recycling. Using live-cell imaging to monitor individual endosomes and ligand particles in real time, we have discovered a sorting mechanism that takes place prior to early endosome entry. We show that early endosomes are in fact comprised of two distinct populations: a dynamic population that is highly mobile on microtubules and matures rapidly toward late endosomes and a static population that matures much more slowly. Several cargos destined for degradation are preferentially targeted to the dynamic endosomes, whereas the recycling ligand transferrin is nonselectively delivered to all early endosomes and effectively enriched in the larger, static population. This pre-early endosome sorting process begins at clathrin-coated vesicles, depends on microtubule-dependent motility, and appears to involve endocytic adaptors.
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There are conflicting reports as to whether LDLR and TfnR are internalized via the same or distinct CCPs.
“there are conflicting reports as to whether LDLR and TfnR are internalized via the same or distinct CCPs (Keyel et al., 2006; Lakadamyali et al., 2006).”
From Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis (2010) · cites this paper as Lakadamyali et al., 2006
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Merrifield, C. J., Perrais, D., & Zenisek, D. (2005) · Cell · doi:10.1016/j.cell.2005.03.015 · Cited by 476 · cited 1×
“Indeed, real-time imaging of endocytic structures, such as the clathrin-coated vesicles, has substantially improved our understanding of their biogenesis (Gaidarov et al., 1999; Merrifield et al., 2002; Ehrlich et al., 2004; Merrifield et al., 2005).”
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Research works printed but not linked: 69
- Anderson, 1977, Role of the coated endocytic vesicle in the uptake of receptor-bound low density lipoprotein in human fibroblasts, Cell, 10, 351, 10.1016/0092-8674(77)90022-8 · DOI · Paper page
- Anderson, 1982, Surface distribution and recycling of the low density lipoprotein receptor as visualized with antireceptor antibodies, J. Cell Biol., 93, 523, 10.1083/jcb.93.3.523 · DOI
- Barbero, 2002, Visualization of Rab9-mediated vesicle transport from endosomes to the trans-Golgi in living cells, J. Cell Biol., 156, 511, 10.1083/jcb.200109030 · DOI
- Bomsel, 1989, Endocytosis in filter-grown madin-darby canine kidney-cells, J. Cell Biol., 109, 3243, 10.1083/jcb.109.6.3243 · DOI
- Bonifacino, 2003, Coated proteins: shaping membrane transport, Nat. Rev. Mol. Cell Biol., 4, 409, 10.1038/nrm1099 · DOI
- Bonifacino, 2003, Signals for sorting of transmembrane proteins to endosomes and lysosomes, Annu. Rev. Biochem., 72, 395, 10.1146/annurev.biochem.72.121801.161800 · DOI · Paper page
- Cao, 1998, Regulated endocytosis of G-protein-coupled receptors by a biochemically and functionally distinct subpopulation of clathrin-coated pits, J. Biol. Chem., 273, 24592, 10.1074/jbc.273.38.24592 · DOI
- Carpenter, 1979, Epidermal growth-factor, Annu. Rev. Biochem., 48, 193, 10.1146/annurev.bi.48.070179.001205 · DOI
- Chavrier, 1990, Localization of low molecular weight GTP binding proteins to exocytic and endocytic compartments, Cell, 62, 317, 10.1016/0092-8674(90)90369-P · DOI · Paper page
- Chen, 2005, The association of epsin with ubiquitinated cargo along the endocytic pathway is negatively regulated by its interaction with clathrin, Proc. Natl. Acad. Sci. USA, 102, 2766, 10.1073/pnas.0409719102 · DOI
- Conner, 2003, Differential requirements for AP-2 in clathrin-mediated endocytosis, J. Cell Biol., 162, 773, 10.1083/jcb.200304069 · DOI · Paper page
- Dautry-Varsat, 1982, pH and the recycling of transferrin during receptor-mediated endocytosis, Proc. Natl. Acad. Sci. USA, 80, 2258, 10.1073/pnas.80.8.2258 · DOI
- Dickson, 1983, Prelysosomal divergence of transferrin and epidermal growth factor during receptor-mediated endocytosis, J. Biochem., 22, 5667, 10.1021/bi00293a033 · DOI
- Dunn, 1989, Iterative fractionation of recycling receptors from lysosomally destined ligands in an early sorting endosome, J. Cell Biol., 109, 3303, 10.1083/jcb.109.6.3303 · DOI · Paper page
- Ehrlich, 2004, Endocytosis by random initiation and stabilization of clathrin-coated pits, Cell, 118, 591, 10.1016/j.cell.2004.08.017 · DOI · Paper page
- Gaidarov, 1999, Spatial control of coated-pit dynamics in living cells, Nat. Cell Biol., 1, 1, 10.1038/8971 · DOI
- Ghosh, 1994, Quantification of low density lipoprotein and transferrin endocytic sorting in HEp2 cells using confocal microscopy, J. Cell Sci., 107, 2177, 10.1242/jcs.107.8.2177 · DOI · Paper page
- Goldstein, 1985, Receptor-mediated endocytosis: concepts emerging from the LDL receptor system, Annu. Rev. Cell Biol., 1, 1, 10.1146/annurev.cb.01.110185.000245 · DOI · Paper page
- Gruenberg, 2001, The endocytic pathway: a mosaic of domains, Nat. Rev. Mol. Cell Biol., 2, 721, 10.1038/35096054 · DOI
- Gruenberg, 2004, The biogenesis of multivesicular endosomes, Nat. Rev. Mol. Cell Biol., 5, 317, 10.1038/nrm1360 · DOI
- Hicke, 2003, Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins, Annu. Rev. Cell Biol., 19, 141, 10.1146/annurev.cellbio.19.110701.154617 · DOI
- Hinrichsen, 2003, Effect of clathrin heavy chain- and α-adaptin specific small inhibitory RNAs on endocytic accessory proteins and receptor trafficking in HeLa cells, J. Biol. Chem., 278, 45160, 10.1074/jbc.M307290200 · DOI · Paper page
- Hopkins, 1983, Internalization and processing of transferrin and the transferrin receptor in human carcinoma A431 cells, J. Cell Biol., 97, 508, 10.1083/jcb.97.2.508 · DOI
- Huang, 2004, Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interference, J. Biol. Chem., 279, 16657, 10.1074/jbc.C400046200 · DOI
- Hughson, 1990, Endocytic pathways in polarized caco-2 cells—identification of an endosomal compartment accessible from both apical and basolateral surfaces, J. Cell Biol., 110, 337, 10.1083/jcb.110.2.337 · DOI
- Hussain, 2003, A role for epsin N-terminal homology/AP180 N-terminal homology (ENTH/ANTH) domains in tubulin binding, J. Biol. Chem., 278, 28823, 10.1074/jbc.M300995200 · DOI
- Jiang, 2003, Epidermal growth factor receptor internalization through clathrin-coated pits requires CbI RING finger and proline-rich domains but not receptor polyubiquitylation, Traffic, 4, 529, 10.1034/j.1600-0854.2003.t01-1-00109.x · DOI
- Kittel, 1999, Ultrastructural localization of beta-arrestin-1 and -2 in rat lumbar spinal cord, J. Comp. Neurol., 412, 649, 10.1002/(SICI)1096-9861(19991004)412:4<649::AID-CNE6>3.0.CO;2-4 · DOI
- Lakadamyali, 2003, Visualizing infection of individual influenza viruses, Proc. Natl. Acad. Sci. USA, 100, 9280, 10.1073/pnas.0832269100 · DOI
- Marchese, 2003, The ins and outs of G protein-coupled receptor trafficking, Trends Biochem. Sci., 28, 369, 10.1016/S0968-0004(03)00134-8 · DOI
- Matlin, 1981, Infectious entry pathway of influenza virus in a canine kidney-cell line, J. Cell Biol., 91, 601, 10.1083/jcb.91.3.601 · DOI
- Mayor, 1993, Sorting of membrane components from endosomes and subsequent recycling to the cell serface occurs by a bulk flow process, J. Cell Biol., 121, 1257, 10.1083/jcb.121.6.1257 · DOI · Paper page
- Mellman, 1996, Endocytosis and molecular sorting, Annu. Rev. Cell Dev. Biol., 12, 575, 10.1146/annurev.cellbio.12.1.575 · DOI
- Mellman, 2000, The road taken: past and future foundations of membrane traffic, Cell, 100, 99, 10.1016/S0092-8674(00)81687-6 · DOI
- Mellman, 1986, Acidification of the endocytic and exocytic pathways, Annu. Rev. Biochem., 55, 663, 10.1146/annurev.bi.55.070186.003311 · DOI
- Merrifield, 2002, Imaging actin and dynamin recruitment during invagination of single clathrin-coated pits, Nat. Cell Biol., 4, 691, 10.1038/ncb837 · DOI · Paper page
- Morris, 2001, Disabled-2 colocalizes with LDLR in clathrin-coated pits and interacts with AP-2, Traffic, 2, 111, 10.1034/j.1600-0854.2001.020206.x · DOI · Paper page
- Motley, 2003, Clathrin-mediated endocytosis in AP-2-depleted cells, J. Cell Biol., 162, 909, 10.1083/jcb.200305145 · DOI
- Mukherjee, 1999, Endocytic sorting of lipid analogues differing solely in the chemistry of their hydrophobic tail, J. Cell Biol., 144, 1271, 10.1083/jcb.144.6.1271 · DOI
- Mundigl, 1993, Synaptic vesicle proteins and early endosomes in cultured hippocampal-neurons—differential-effects of brefeldin-A in axon and dendrites, J. Cell Biol., 122, 1207, 10.1083/jcb.122.6.1207 · DOI
- Nesterov, 1999, Inhibition of the receptor-binding function of clathrin adaptor protein AP-2 by dominant-negative mutant μ2 subunit and its effects on endocytosis, EMBO J., 18, 2489, 10.1093/emboj/18.9.2489 · DOI
- Nielsen, 1999, Rab 5 regulates motility of early endosomes on microtubules, Nat. Cell Biol., 1, 376, 10.1038/14075 · DOI
- Parton, 1992, Axonal and dendritic endocytic pathways in cultured neurons, J. Cell Biol., 119, 123, 10.1083/jcb.119.1.123 · DOI
- Pelkmans, 2003, Insider information: what viruses tell us about endocytosis, Curr. Opin. Cell Biol., 15, 414, 10.1016/S0955-0674(03)00081-4 · DOI
- Pelkmans, 2004, Caveolin-stabilized membrane domains as multifunctional transport and sorting devices in endocytic membrane traffic, Cell, 118, 767, 10.1016/j.cell.2004.09.003 · DOI
- Pfeffer, 2004, Targeting RAB GTPases to distinct membrane compartments, Nat. Rev. Mol. Cell Biol., 5, 886, 10.1038/nrm1500 · DOI
- Rink, 2005, Rab conversion as a mechanism of progression from early to late endosome, Cell, 122, 735, 10.1016/j.cell.2005.06.043 · DOI
- Robinson, 2004, Adaptable adaptors for coated vesicles, Trends Cell Biol., 14, 167, 10.1016/j.tcb.2004.02.002 · DOI
- Rust, 2004, Assembly of endocytic machinery around individual influenza viruses during viral entry, Nat. Struct. Mol. Biol., 11, 567, 10.1038/nsmb769 · DOI
- Schmid, 1997, Clathrin-coated vesicle formation and protein sorting, Annu. Rev. Biochem., 66, 511, 10.1146/annurev.biochem.66.1.511 · DOI
- Sheff, 1999, The receptor recycling pathways contains two distinct populations of early endosomes with different sorting function, J. Cell Biol., 145, 123, 10.1083/jcb.145.1.123 · DOI · Paper page
- Sheff, 2002, Transferrin receptor recycling in the absence of perinuclear recycling endosomes, J. Cell Biol., 156, 797, 10.1083/jcb.20111048 · DOI
- Sieczkarski, 2002, Influenza virus can enter and infect cells in the absence of clathrin-mediated endocytosis, J. Virol., 76, 10455, 10.1128/JVI.76.20.10455-10464.2002 · DOI
- Sigismund, 2005, Clathrin-independent endocytosis of ubiquitinated cargos, Proc. Natl. Acad. Sci. USA, 102, 2760, 10.1073/pnas.0409817102 · DOI · Paper page
- Sonnichsen, 2000, Distinct membrane domains on endosomes in the recycling pathway visualized by multicolor imaging of Rab4, Rab5 and Rab11, J. Cell Biol., 149, 901, 10.1083/jcb.149.4.901 · DOI · Paper page
- Sorkin, 2004, Cargo recognition during clathrin-mediated endocytosis: a team effort, Curr. Opin. Cell Biol., 16, 392, 10.1016/j.ceb.2004.06.001 · DOI
- Stoorvogel, 1991, Late endosomes derive from early endosomes by maturation, Cell, 65, 417, 10.1016/0092-8674(91)90459-C · DOI
- Tanowitz, 2003, A novel endocytic recycling signal that distinguishes the membrane trafficking of naturally occurring opioid receptors, J. Biol. Chem., 278, 45978, 10.1074/jbc.M304504200 · DOI · Paper page
- Traub, 2003, Sorting it out: AP-2 and alternate clathrin adaptors in endocytic cargo selection, J. Cell Biol., 163, 203, 10.1083/jcb.200309175 · DOI
- Trowbridge, 1993, Signal dependent membrane protein trafficking in the endocytic pathway, Annu. Rev. Cell Biol., 9, 129, 10.1146/annurev.cb.09.110193.001021 · DOI
- Ullrich, 1996, Rab11 regulates recycling through pericentriolar recycling endosomes, J. Cell Biol., 135, 913, 10.1083/jcb.135.4.913 · DOI · Paper page
- van Leuven, 1980, Primary amines inhibit recycling of alpha-2m receptors in fibroblasts, Cell, 20, 37, 10.1016/0092-8674(80)90232-9 · DOI
- Vonderheit, 2005, Rab7 associates with early endosomes to mediate sorting and transport of semliki forest virus to late endosomes, PLoS Biol., 3, e233, 10.1371/journal.pbio.0030233 · DOI
- Wall, 1980, The galactose-specific recognition system of mammalian liver—the route of ligand internalization in rat hepatocytes, Cell, 21, 79, 10.1016/0092-8674(80)90116-6 · DOI
- Watanabe, 1999, Internalization and sorting of plasma membrane sphingolipid analogues in differentiating oligodendrocytes, J. Neurochem., 73, 1375, 10.1046/j.1471-4159.1999.0731375.x · DOI
- Wei, 1998, GLUT4 and transferrin receptor are differentially sorted along the endocytic pathway in CHO cells, J. Cell Biol., 140, 565, 10.1083/jcb.140.3.565 · DOI
- Yamashiro, 1987, Acidification of morphologically distinct endosomes in mutant and wild-type chinese-hamster ovary cells, J. Cell Biol., 105, 2723, 10.1083/jcb.105.6.2723 · DOI
- Yishimura, 1984, Uncoating of influenza virus in endosomes, J. Virol., 51, 497, 10.1128/jvi.51.2.497-504.1984 · DOI
- Zerial, 2001, Rab proteins as membrane organizers, Mol. Cell. Biol., 2, 107
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Metadata
- Authors
- Lakadamyali, M., Rust, M. J., & Zhuang, X.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 124
- Issue
- 5
- Pages
- 997-1009
- ISSN
- 0092-8674
- Cited by
- 508
- References
- 1
- Language
- en
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2731 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
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