The Endocytic Pathway

  • Elizabeth ConibearEmail author
  • Yuen Yi C. Tam
Part of the Molecular Biology Intelligence Unit book series (MBIU)


As the interface between the intracellular and extracellular environments, the plasma membrane forms a barrier to the uptake of nutrients and other macromolecules as well as a defense against pathogens. Specialized endocytic mechanisms direct the internalization of plasma membrane components, together with extracellular fluid, into vesicles that bud into the cytoplasm and deliver their contents to endosomes. Endosomal sorting processes lead to the delivery of some internalized molecules to the lysosome for degradation, while others are recycled back to the cell surface or routed to other intracellular compartments, including those of the secretory pathway. Here, we summarize the main mechanisms of internalization, describe the endocytic compartments and the pathways that connect them, and examine the processes that direct sorting along these different pathways.


Lipid Raft Early Endosome Late Endosome Retrograde Transport Endocytic Pathway 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Aderem A, Underhill DM. Mechanisms of phagocytosis in macrophages. Annu Rev Immunol 1999; 17:593–623.PubMedCrossRefGoogle Scholar
  2. 2.
    Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature 2003; 422(6927):37–44.PubMedCrossRefGoogle Scholar
  3. 3.
    Roth TF, Porter KR. Yolk protein uptake in the oocyte of the mosquito aedes aegypti. L. J Cell Biol 1964; 20:313–32.PubMedCrossRefGoogle Scholar
  4. 4.
    Pearse BM. Clathrin: A unique protein associated with intracellular transfer of membrane by coated vesicles. Proc Natl Acad Sci USA 1976; 73(4):1255–59.PubMedCrossRefGoogle Scholar
  5. 5.
    Conner SD, Schmid SL. Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis. J Cell Biol 2002; 156(5):921–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Owen DJ. Linking endocytic cargo to clathrin: Structural and functional insights into coated vesicle formation. Biochem Soc Trans 2004; 32(Pt 1):1–14.PubMedCrossRefGoogle Scholar
  7. 7.
    Hinrichsen L, Harborth J, Andrees L et al. Effect of clathrin heavy chain-and alpha-adaptin-specific small inhibitory RNAs on endocytic accessory proteins and receptor trafficking in HeLa cells. J Biol Chem 2003; 278(46):45160–70.PubMedCrossRefGoogle Scholar
  8. 8.
    Jackson AP, Flett A, Smythe C et al. Clathrin promotes incorporation of cargo into coated pits by activation of the AP2 adaptor micro2 kinase. J Cell Biol 2003; 163(2):231–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Motley A, Bright NA, Seaman MN et al. Clathrin-mediated endocytosis in AP-2-depleted cells. J Cell Biol 2003; 162(5):909–18.PubMedCrossRefGoogle Scholar
  10. 10.
    Huang KM, D’Hondt K, Riezman H et al. Clathrin functions in the absence of heterotetrameric adaptors and AP180-related proteins in yeast. EMBO J 1999; 18(14):3897–908.PubMedCrossRefGoogle Scholar
  11. 11.
    Yeung BG, Phan HL, Payne GS. Adaptor complex-independent clathrin function in yeast. Mol Biol Cell 1999; 10(11):3643–59.PubMedGoogle Scholar
  12. 12.
    Traub LM. Sorting it out: AP-2 and alternate clathrin adaptors in endocytic cargo selection. J Cell Biol 2003; l63(2):203–8.CrossRefGoogle Scholar
  13. 13.
    Confalonieri S, Salcini AE, Puri C et al. Tyrosine phosphorylation of Epsl5 is required for ligand-regulated, but not constitutive, endocytosis. J Cell Biol 2000; 150(4):905–12.PubMedCrossRefGoogle Scholar
  14. 14.
    Zhang B, Zelhof AC. Amphiphysins: Raising the BAR for synaptic vesicle recycling and membrane dynamics. Bin-Amphiphysin-Rvsp. Traffic 2002; 3(7):452–60.PubMedCrossRefGoogle Scholar
  15. 15.
    Benmerah A, Bayrou M, Cerf-Bensussan N et al. Inhibition of clathrin-coated pit assembly by an Epsl5 mutant. J Cell Sci 1999; 112(Pt 9):1303–11.PubMedGoogle Scholar
  16. 16.
    Chen H, Fre S, Slepnev VI et al. Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis. Nature 1998; 394(6695):793–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Sever S, Damke H, Schmid SL. Garrotes, springs, ratchets, and whips: Putting dynamin models to the test. Traffic 2000; 1(5):385–92.PubMedCrossRefGoogle Scholar
  18. 18.
    Merrifield CJ, Perrais D, Zenisek D. Coupling between clathrin-coated-pit invagination, cortactin recruitment, and membrane scission observed in live cells. Cell 2005; 121(4):593–606.PubMedCrossRefGoogle Scholar
  19. 19.
    Damke H, Baba T, Warnock DE et al. Induction of mutant dynamin specifically blocks endocytic coated vesicle formation. J Cell Biol 1994; 127(4):915–34.PubMedCrossRefGoogle Scholar
  20. 20.
    Cremona O, De Camilli P. Phosphoinositides in membrane traffic at the synapse. J Cell Sci 2001; H4(Pt 6):1041–52.Google Scholar
  21. 21.
    Lemmon SK. Clathrin uncoating: Auxilin comes to life. Curr Biol 2001; 11(2):R49–52.PubMedCrossRefGoogle Scholar
  22. 22.
    Kurzchalia TV, Dupree P, Parton RG et al. VIP21, a 21-kD membrane protein is an integral component of trans-Golgi-network-derived transport vesicles. J Cell Biol 1992; 118(5):1003–14.PubMedCrossRefGoogle Scholar
  23. 23.
    Rothberg KG, Heuser JE, Donzell WC et al. Caveolin, a protein component of caveolae membrane coats. Cell 1992; 68(4):673–82.PubMedCrossRefGoogle Scholar
  24. 24.
    Anderson R G. The caveolae membrane system. Annu Rev Biochem 1998; 67:199–225.PubMedCrossRefGoogle Scholar
  25. 25.
    Drab M, Verkade P, Elger M et al. Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science 2001; 293(5539):2449–52.PubMedCrossRefGoogle Scholar
  26. 26.
    Le PU, Guay G, Altschuler Y et al. Caveolin-1 is a negative regulator of caveolae-mediated endocytosis to the endoplasmic reticulum. J Biol Chem 2002; 277(5):3371–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Pelkmans L. Secrets of caveolae-and lipid raft-mediated endocytosis revealed by mammalian viruses. Biochim Biophys Acta 2005; 1746(3):295–304.PubMedCrossRefGoogle Scholar
  28. 28.
    Fra AM, Williamson E, Simons K et al. De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin. Proc Natl Acad Sci USA 1995; 92(19):8655–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Thomsen P, Roepstorff K, Stahlhut M et al. Caveolae are highly immobile plasma membrane microdomains, which are not involved in constitutive endocytic trafficking. Mol Biol Cell 2002; 13(1):238–50.PubMedCrossRefGoogle Scholar
  30. 30.
    Parton RG, Joggerst B, Simons K. Regulated internalization of caveolae. J Cell Biol 1994; 127(5):1199–215.PubMedCrossRefGoogle Scholar
  31. 31.
    Pelkmans L, Puntener D, Helenius A. Local actin polymerization and dynamin recruitment in SV40-induced internalization of caveolae. Science 2002; 296(5567):535–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Pelkmans L, Fava E, Grabner H et al. Genome-wide analysis of human kinases in clathrin-and caveolae/raft-mediated endocytosis. Nature 2005; 436(7047):78–86.PubMedCrossRefGoogle Scholar
  33. 33.
    Pelkmans L, Zerial M. Kinase-regulated quantal assemblies and kiss-and-run recycling of caveolae. Nature 2005; 436(7047):128–33.PubMedCrossRefGoogle Scholar
  34. 34.
    Pelkmans L, Kartenbeck J, Helenius A. Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nat Cell Biol 2001; 3(5):473–83.PubMedCrossRefGoogle Scholar
  35. 35.
    Pelkmans L, Burli T, Zerial M et al. Caveolin-stabilized membrane domains as multifunctional transport and sorting devices in endocytic membrane traffic. Cell 2004; 118(6):767–80.PubMedCrossRefGoogle Scholar
  36. 36.
    Henley JR, Krueger EW, Oswald BJ et al. Dynamin-mediated internalization of caveolae. J Cell Biol 1998; 141(1):85–99.PubMedCrossRefGoogle Scholar
  37. 37.
    Oh P, Mcintosh DP, Schnitzer JE. Dynamin at the neck of caveolae mediates their budding to form transport vesicles by GTP-driven fission from the plasma membrane of endothelium. J Cell Biol 1998; 141 (1):101–14.PubMedCrossRefGoogle Scholar
  38. 38.
    Schnitzer JE, Liu J, Oh P. Endothelial caveolae have the molecular transport machinery for vesicle budding, docking, and fusion including VAMP, NSF, SNAP, annexins, and GTPases. J Biol Chem 1995; 270(24):14399–404.PubMedCrossRefGoogle Scholar
  39. 39.
    Melkonian KA, Ostermeyer AG, Chen JZ et al. Role of lipid modifications in targeting proteins to detergent-resistant membrane rafts. Many raft proteins are acylated, while few are prenylated. J Biol Chem 1999; 274(6):3910–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Lamaze C, Dujeancourt A, Baba T et al. Interleukin 2 receptors and detergent-resistant membrane domains define a clathrin-independent endocytic pathway. Mol Cell 2001; 7(3):661–71.PubMedCrossRefGoogle Scholar
  41. 41.
    Nichols BJ, Kenworthy AK, Polishchuk RS et al. Rapid cycling of lipid raft markers between the cell surface and Golgi complex. J Cell Biol 2001; 153(3):529–41.PubMedCrossRefGoogle Scholar
  42. 42.
    Puri V, Watanabe R, Singh RD et al. Clathrin-dependent and-independent internalization of plasma membrane sphingolipids initiates two Golgi targeting pathways. J Cell Biol 2001; 154(3):535–47.PubMedCrossRefGoogle Scholar
  43. 43.
    Nabi IR, Le PU. Caveolae/raft-dependent endocytosis. J Cell Biol 2003; 161(4):673–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Nichols B. Caveosomes and endocytosis of lipid rafts. J Cell Sci 2003; H6(Pt 23):4707–14.CrossRefGoogle Scholar
  45. 45.
    Munro S. Lipid rafts: Elusive or illusive? Cell 2003; 115(4):377–88.PubMedCrossRefGoogle Scholar
  46. 46.
    Mukherjee S, Ghosh R N, Maxfield FR. Endocytosis. Physiol Rev 1997; 77(3):759–803.PubMedGoogle Scholar
  47. 47.
    Mineo C, Gill GN, Anderson RG. Regulated migration of epidermal growth factor receptor from caveolae. J Biol Chem 1999; 274(43):30636–43.PubMedCrossRefGoogle Scholar
  48. 48.
    Sandvig K, Olsnes S, Brown JE et al. Endocytosis from coated pits of Shiga toxin: A glycolipid-binding protein from Shigella dysenteriae 1. J Cell Biol 1989; 108(4):1331–43.PubMedCrossRefGoogle Scholar
  49. 49.
    Torgersen ML, Skretting G, van Deurs B et al. Internalization of cholera toxin by different endocytic mechanisms. J Cell Sci 2001; H4(Pt 20):3737–47.Google Scholar
  50. 50.
    Sabharanjak S, Sharma P, Parton RG et al. GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42-regulated, clathrin-independent pinocytic pathway. Dev Cell 2002; 2(4):411–23.PubMedCrossRefGoogle Scholar
  51. 51.
    Guha A, Sriram V, Krishnan KS et al. Shibire mutations reveal distinct dynamin-independent and-dependent endocytic pathways in primary cultures of Drosophila hemocytes. J Cell Sci 2003; 116(Pt 16):3373–86.PubMedCrossRefGoogle Scholar
  52. 52.
    Mayor S, Rothberg KG, Maxfield FR. Sequestration of GPI-anchored proteins in caveolae triggered by cross-linking. Science 1994; 264(5167):1948–51.PubMedCrossRefGoogle Scholar
  53. 53.
    Nobes C, Marsh M. Dendritic cells: New roles for Cdc42 and Rac in antigen uptake? Curr Biol 2000; 10(20):R739–R741.PubMedCrossRefGoogle Scholar
  54. 54.
    Nothwehr SF, Conibear E, Stevens TH. Golgi and vacuolar membrane proteins reach the vacuole in vpsl mutant yeast cells via the plasma membrane. J Cell Biol 1995; 129(1):35–46.PubMedCrossRefGoogle Scholar
  55. 55.
    Payne GS, Baker D, van Tuinen E et al. Protein transport to the vacuole and receptor-mediated endocytosis by clathrin heavy chain-deficient yeast. J Cell Biol 1988; 06(5):1453–61.CrossRefGoogle Scholar
  56. 56.
    Tan PK, Davis NG, Sprague GF et al. Clathrin facilitates the internalization of seven transmembrane segment receptors for mating pheromones in yeast. J Cell Biol 1993; 23(6 Pt 2):1707–16.CrossRefGoogle Scholar
  57. 57.
    Newpher TM, Smith RP, Lemmon V et al. In vivo dynamics of clathrin and its adaptor-dependent recruitment to the actin-based endocytic machinery in yeast. Dev Cell 2005; (1):87–98.CrossRefGoogle Scholar
  58. 58.
    Kaksonen M, Toret CP, Drubin DG. A modular design for the clathrin-and actin-mediated endocytosis machinery. Cell 2005; 23(2):305–20.CrossRefGoogle Scholar
  59. 59.
    Merrifield CJ, Feldman ME, Wan L et al. Imaging actin and dynamin recruitment during invagination of single clathrin-coated pits. Nat Cell Biol 2002; (9):691–8.CrossRefGoogle Scholar
  60. 60.
    Perrais D, Merrifield CJ. Dynamics of endocytic vesicle creation. Dev Cell 2005; (5):581–92.CrossRefGoogle Scholar
  61. 61.
    Woodman PC. Biogenesis of the sorting endosome: The role of Rab 5. Traffic 2000; (9):695–701.CrossRefGoogle Scholar
  62. 62.
    Presley JF, Mayor S, McGraw TE et al. Bafilomycin Al treatment retards transferrin receptor recycling more than bulk membrane recycling. J Biol Chem 1997; 72(21):13929–36.CrossRefGoogle Scholar
  63. 63.
    Johnson LS, Dunn KW, Pytowski B et al. Endosome acidification and receptor trafficking: bafilomycin Al slows receptor externalization by a mechanism involving the receptor’s internalization motif. Mol Biol Cell 1993; (12):1251–66.Google Scholar
  64. 64.
    Dunn KW, McGraw TE, Maxfield FR. Iterative fractionation of recycling receptors from lysosomally destined ligands in an early sorting endosome. J Cell Biol 1989; 109(6 Pt 2):3303–14.PubMedCrossRefGoogle Scholar
  65. 65.
    Mayor S, Presley JF, Maxfield FR. Sorting of membrane components from endosomes and subsequent recycling to the cell surface occurs by a bulk flow process. J Cell Biol 1993; 121(6):1257–69.PubMedCrossRefGoogle Scholar
  66. 66.
    Griffiths G, Matteoni R, Back R et al. Characterization of the cation-independent mannose 6-phosphate receptor-enriched prelysosomal compartment in NRK cells. J Cell Sci 1990; 95(Pt 3):441–61.PubMedGoogle Scholar
  67. 67.
    Futter CE, Pearse A, Hewlett LJ et al. Multivesicular endosomes containing internalized EGF-EGF receptor complexes mature and then fuse directly with lysosomes. J Cell Biol 1996; 132(6):1011–23.PubMedCrossRefGoogle Scholar
  68. 68.
    Felder S, Miller K, Moehren G et al. Kinase activity controls the sorting of the epidermal growth factor receptor within the multivesicular body. Cell 1990; 61(4):623–34.PubMedCrossRefGoogle Scholar
  69. 69.
    Katzmann DJ, Odorizzi G, Emr SD. Receptor downregulation and multivesicular-body sorting. Nat Rev Mol Cell Biol 2002; 3(12):893–905.PubMedCrossRefGoogle Scholar
  70. 70.
    Escola JM, Kleijmeer MJ, Stoorvogel W et al. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem 1998; 273(32):20121–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Denzer K, Kleijmeer MJ, Heijnen HF et al. Exosome: From internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci 2000; 113(Pt 19):3365–74.PubMedGoogle Scholar
  72. 72.
    Piper RC, Luzio JP. Late endosomes: Sorting and partitioning in multivesicular bodies. Traffic 2001; 2(9):612–21.PubMedCrossRefGoogle Scholar
  73. 73.
    Longva KE, Blystad FD, Stang E et al. Ubiquitination and proteasomal activity is required for transport of the EGF receptor to inner membranes of multivesicular bodies. J Cell Biol 2002; 156(5):843–54.PubMedCrossRefGoogle Scholar
  74. 74.
    Reggiori F, Black MW, Pelham HR. Polar transmembrane domains target proteins to the interior of the yeast vacuole. Mol Biol Cell 2000; 11(11):3737–49.PubMedGoogle Scholar
  75. 75.
    Reggiori F, Pelham HR. A transmembrane ubiquitin ligase required to sort membrane proteins into multivesicular bodies. Nat Cell Biol 2002; 4(2):117–23.PubMedCrossRefGoogle Scholar
  76. 76.
    Reggiori F, Pelham HR. Sorting of proteins into multivesicular bodies: Ubiquitin-dependent and-independent targeting. EMBO J 2001; 20(18):5176–86.PubMedCrossRefGoogle Scholar
  77. 77.
    Vida TA, Emr SD. A new vital stain for visualizing vacuolar membrane dynamics and endocytosis in yeast. J Cell Biol 1995; 128(5):779–92.PubMedCrossRefGoogle Scholar
  78. 78.
    Grant AM, Hanson PK, Malone L et al. NBD-labeled phosphatidylcholine and phosphatidyletha-nolamine are internalized by transbilayer transport across the yeast plasma membrane. Traffic 2001; 2(1):37–50.PubMedCrossRefGoogle Scholar
  79. 79.
    Kobayashi T, Stang E, Fang KS et al. A lipid associated with the antiphospholipid syndrome regulates endosome structure and function. Nature 1998; 392(6672):193–7.PubMedCrossRefGoogle Scholar
  80. 80.
    Gillooly DJ, Morrow IC, Lindsay M et al. Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cells. EMBO J 2000; 19(17):4577–88.PubMedCrossRefGoogle Scholar
  81. 81.
    Katzmann DJ, Stefan CJ, Babst M et al. Vps27 recruits ESCRT machinery to endosomes during MVB sorting. J Cell Biol 2003; 162(3):413–23.PubMedCrossRefGoogle Scholar
  82. 82.
    Yeo SC, Xu L, Ren J et al. Vps20p and Vtalp interact with Vps4p and function in multivesicular body sorting and endosomal transport in Saccharomyces cerevisiae. J Cell Sci 2003; H6(Pt 19): 3957–70.CrossRefGoogle Scholar
  83. 83.
    Bilodeau PS, Winistorfer SC, Kearney WR et al. Vps27-Hsel and ESCRT-I complexes cooperate to increase efficiency of sorting ubiquitinated proteins at the endosome. J Cell Biol 2003; 163(2):237–43.PubMedCrossRefGoogle Scholar
  84. 84.
    Bache KG, Brech A, Mehlum A et al. Hrs regulates multivesicular body formation via ESCRT recruitment to endosomes. J Cell Biol 2003; 162(3):435–42.PubMedCrossRefGoogle Scholar
  85. 85.
    Bishop N, Woodman P. ATPase-defective mammalian VPS4 localizes to aberrant endosomes and impairs cholesterol trafficking. Mol Biol Cell 2000; 11(1):227–39.PubMedGoogle Scholar
  86. 86.
    Bishop N, Woodman P. TSGlOl/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes. J Biol Chem 2001; 276(15):11735–42.PubMedCrossRefGoogle Scholar
  87. 87.
    Nielsen E, Christoforidis S, Uttenweiler-Joseph S et al. Rabenosyn-5, a novel Rab5 effector, is complexed with hVPS45 and recruited to endosomes through a FYVE finger domain. J Cell Biol 2000; 151(3):601–12.PubMedCrossRefGoogle Scholar
  88. 88.
    Lewis MJ, Nichols BJ, Prescianotto-Baschong C et al. Specific retrieval of the exocytic SNARE Snclp from early yeast endosomes. Mol Biol Cell 2000; ll(l):23–38.Google Scholar
  89. 89.
    Pelham HR. Insights from yeast endosomes. Curr Opin Cell Biol 2002; l4(4):454–62.CrossRefGoogle Scholar
  90. 90.
    Antonin W, Holroyd C, Fasshauer D et al. A SNARE complex mediating fusion of late endosomes defines conserved properties of SNARE structure and function. EMBO J 2000; 19(23):6453–64.PubMedCrossRefGoogle Scholar
  91. 91.
    Luzio JP, Rous BA, Bright NA et al. Lysosome-endosome fusion and lysosome biogenesis. J Cell Sci 2000; 113(Pt 9):1515–24.PubMedGoogle Scholar
  92. 92.
    Mullock BM, Smith CW, Ihrke G et al. Syntaxin 7 is localized to late endosome compartments, associates with vamp 8, and Is required for late endosome-lysosome fusion. Mol Biol Cell 2000; ll(9):3137–53.Google Scholar
  93. 93.
    Bonifacino JS. The GGA proteins: Adaptors on the move. Nat Rev Mol Cell Biol 2004; 5(l):23–32.PubMedCrossRefGoogle Scholar
  94. 94.
    Puertollano R, Aguilar RC, Gorshkova I et al. Sorting of mannose 6-phosphate receptors mediated by the GGAs. Science 2001; 292(5522):1712–16.PubMedCrossRefGoogle Scholar
  95. 95.
    Zhu Y, Doray B, Poussu A et al. Binding of GGA2 to the lysosomal enzyme sorting motif of the mannose 6-phosphate receptor. Science 2001; 292(5522):1716–8.PubMedCrossRefGoogle Scholar
  96. 96.
    Meyer C, Zizioli D, Lausmann S et al. mulA-adaptin-deficient mice: Lethality, loss of AP-1 binding and rerouting of mannose 6-phosphate receptors. EMBO J 2000; 19(10):2193–203.CrossRefGoogle Scholar
  97. 97.
    Press B, Feng Y, Hoflack B et al. Mutant Rab7 causes the accumulation of cathepsin D and cation-independent mannose 6-phosphate receptor in an early endocytic compartment. J Cell Biol 1998; 140(5): 1075–89.CrossRefGoogle Scholar
  98. 98.
    Costaguta G, Stefan CJ, Bensen ES et al. Yeast Gga coat proteins function with clathrin in Golgi to endosome transport. Mol Biol Cell 2001; 12(6):1885–96.PubMedGoogle Scholar
  99. 99.
    Sheff DR, Daro EA, Hull M et al. The receptor recycling pathway contains two distinct populations of early endosomes with different sorting functions. J Cell Biol 1999; 145(1):123–39.CrossRefGoogle Scholar
  100. 100.
    Hao M, Maxfield FR. Characterization of rapid membrane internalization and recycling. J Biol Chem 2000; 275 (20):15279–86.PubMedCrossRefGoogle Scholar
  101. 101.
    Ghosh RN, Mallet WG, Soe TT et al. An endocytosed TGN38 chimeric protein is delivered to the TGN after trafficking through the endocytic recycling compartment in CHO cells. J Cell Biol 1998; l42(4):923–36.CrossRefGoogle Scholar
  102. 102.
    Mallard F, Antony C, Tenza D et al. Direct pathway from early/recycling endosomes to the Golgi 1apparatus revealed through the study of shiga toxin B-fragment transport. J Cell Biol 1998; 1143(4):973–90.CrossRefGoogle Scholar
  103. 103.
    Wilcke M, Johannes L, Galli T et al. Rabll regulates the compartmentalization of early endosomes required for efficient transport from early endosomes to the trans-golgi network. J Cell Biol 2000; 151(6):1207–20.PubMedCrossRefGoogle Scholar
  104. 104.
    Lin SX, Grant B, Hirsh D et al. Rme-1 regulates the distribution and function of the endocytic recycling compartment in mammalian cells. Nat Cell Biol 2001; 3(6):567–72.PubMedCrossRefGoogle Scholar
  105. 105.
    Jing SQ, Spencer T, Miller K et al. Role of the human transferrin receptor cytoplasmic domain in endocytosis: Localization of a specific signal sequence for internalization. J Cell Biol 1990; 110(2):283–94.PubMedCrossRefGoogle Scholar
  106. 106.
    Gruenberg J. The endocytic pathway: A mosaic of domains. Nat Rev Mol Cell Biol 2001; 2(10):721–30.PubMedCrossRefGoogle Scholar
  107. 107.
    Mayor S, Sabharanjak S, Maxfield FR. Cholesterol-dependent retention of GPI-anchored proteins in endosomes. EMBO J 1998; 17(16):4626–38.PubMedCrossRefGoogle Scholar
  108. 108.
    Sonnichsen B, De Renzis S, Nielsen E et al. Distinct membrane domains on endosomes in the recycling pathway visualized by multicolor imaging of Rab4, Rab5, and Rabll. J Cell Biol 2000; 149(4):901–14.PubMedCrossRefGoogle Scholar
  109. 109.
    de Renzis S, Sonnichsen B, Zerial M. Divalent Rab effectors regulate the sub-compartmental organization and sorting of early endosomes. Nat Cell Biol 2002; 4(2):124–33.PubMedCrossRefGoogle Scholar
  110. 110.
    Wiederkehr A, Avaro S, Prescianotto-Baschong C et al. The F-box protein Rcylp is involved in endocytic membrane traffic and recycling out of an early endosome in Saccharomyces cerevisiae. J Cell Biol 2000; 149(2):397–410.PubMedCrossRefGoogle Scholar
  111. 111.
    Chen L, Davis NG. Recycling of the yeast a-factor receptor. J Cell Biol 2000; 151(3):731–8.PubMedCrossRefGoogle Scholar
  112. 112.
    Chen SH, Chen S, Tokarev AA et al. Ypt31/32 GTPases and their novel F-box effector protein Rcyl regulate protein recycling. Mol Biol Cell 2005; 16(l):178–92.PubMedGoogle Scholar
  113. 113.
    Jedd G, Mulholland J, Segev N. Two new Ypt GTPases are required for exit from the yeast trans-Golgi compartment. J Cell Biol 1997; 137(3):563–80.PubMedCrossRefGoogle Scholar
  114. 114.
    Ortiz D, Medkova M, Walch-Solimena C et al. Ypt32 recruits the Sec4p guanine nucleotide exchange factor, Sec2p, to secretory vesicles; evidence for a Rab cascade in yeast. J Cell Biol 2002; 157(6):1005–15.PubMedCrossRefGoogle Scholar
  115. 115.
    Mallard F, Tang BL, Galli T et al. Early/recycling endosomes-to-TGN transport involves two SNARE complexes and a Rab6 isoform. J Cell Biol 2002; 156(4):653–64.PubMedCrossRefGoogle Scholar
  116. 116.
    Hirst J, Futter CE, Hopkins CR. The kinetics of mannose 6-phosphate receptor trafficking in the endocytic pathway in HEp-2 cells: The receptor enters and rapidly leaves multivesicular endosomes without accumulating in a prelysosomal compartment. Mol Biol Cell 1998; 9(4):809–16.PubMedGoogle Scholar
  117. 117.
    Mallet WG, Maxfield FR. Chimeric forms of furin and TGN38 are transported with the plasma membrane in the trans-Golgi network via distinct endosomal pathways. J Cell Biol 1999; l46(2):345–59.CrossRefGoogle Scholar
  118. 118.
    Seaman MN, McCaffery JM, Emr SD. A membrane coat complex essential for endosome-to-Golgi retrograde transport in yeast. J Cell Biol 1998; 142(3):665–81.PubMedCrossRefGoogle Scholar
  119. 119.
    Seaman MN, Marcusson EG, Cereghino JL et al. Endosome to Golgi retrieval of the vacuolar protein sorting receptor, VpslOp, requires the function of the VPS29, VPS30, and VPS35 gene products. J Cell Biol 1997; 137(l):79–92.PubMedCrossRefGoogle Scholar
  120. 120.
    Seaman MN. Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer. J Cell Biol 2004; 165(1):111–22.PubMedCrossRefGoogle Scholar
  121. 121.
    Arighi CN, Hartnell LM, Aguilar RC et al. Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor. J Cell Biol 2004; 165(l):123–33.PubMedCrossRefGoogle Scholar
  122. 122.
    Carroll KS, Hanna J, Simon I et al. Role of Rab9 GTPase in facilitating receptor recruitment by TIP47. Science 2001; 292(5520):1373–6.PubMedCrossRefGoogle Scholar
  123. 123.
    Barbero P, Bittova L, Pfeffer SR. Visualization of Rab9-mediated vesicle transport from endosomes to the trans-Golgi in living cells. J Cell Biol 2002; 156(3):511–8.PubMedCrossRefGoogle Scholar
  124. 124.
    Krise JP, Sincock PM, Orsel JG et al. Quantitative analysis of TIP47-receptor cytoplasmic domain interactions: Implications for endosome-to-trans Golgi network trafficking. J Biol Chem 2000; 275(33):25188–93.PubMedCrossRefGoogle Scholar
  125. 125.
    Voorhees P, Deignan E, van Donselaar E et al. An acidic sequence within the cytoplasmic domain of furin functions as a determinant of trans-Golgi network localization and internalization from the cell surface. EMBO J 1995; 14(20):4961–75.PubMedGoogle Scholar
  126. 126.
    Crump CM, Xiang Y, Thomas L et al. PACS-1 binding to adaptors is required for acidic cluster motif-mediated protein traffic. EMBO J 2001; 20(9):2191–201.PubMedCrossRefGoogle Scholar
  127. 127.
    Medigeshi GR, Schu P. Characterization of the in vitro retrograde transport of MPR46. Traffic 2003; 4(11):802–11.PubMedCrossRefGoogle Scholar
  128. 128.
    Sandvig K, van Deurs B. Transport of protein toxins into cells: Pathways used by ricin, cholera toxin and Shiga toxin. FEBS Lett 2002; 529(l):49–53.PubMedCrossRefGoogle Scholar
  129. 129.
    Iversen TG, Skretting G, Llorente A et al. Endosome to Golgi transport of ricin is independent of clathrin and of the Rab9-and Rab 11-GTPases. Mol Biol Cell 2001; 12(7):2099–107.PubMedGoogle Scholar
  130. 130.
    Bensen ES, Yeung BG, Payne GS. Riclp and the Ypt6p GTPase function in a common pathway required for localization of trans-Golgi network membrane proteins. Mol Biol Cell 2001; 12(l):13–26.PubMedGoogle Scholar
  131. 131.
    Siniossoglou S, Pelham HR. An effector of Ypt6p binds the SNARE Tlglp and mediates selective fusion of vesicles with late Golgi membranes. EMBO J 2001; 20(21):5991–8.PubMedCrossRefGoogle Scholar
  132. 132.
    Brickner JH, Blanchette JM, Sipos G et al. The Tig SNARE complex is required for TGN homotypic fusion. J Cell Biol 2001; 155(6):969–78.PubMedCrossRefGoogle Scholar
  133. 133.
    Conibear E, Stevens TH. Vps52p, Vps53p, and Vps54p form a novel multisubunit complex required for protein sorting at the yeast late Golgi. Mol Biol Cell 2000; ll(l):305–23.Google Scholar
  134. 134.
    Conibear E, Cleck JN, Stevens TH. Vps51p mediates the association of the GARP (Vps52/53/54) complex with the late Golgi t-SNARE Tlglp. Mol Biol Cell 2003; l4(4):1610–23.CrossRefGoogle Scholar
  135. 135.
    Liewen H, Meinhold-Heerlein I, Oliveira V et al. Characterization of the human GARP (Golgi associated retrograde protein) complex. Exp Cell Res 2005; 306(l):24–34.PubMedCrossRefGoogle Scholar
  136. 136.
    Daro E, Sheff D, Gomez M et al. Inhibition of endosome function in CHO cells bearing a temperature-sensitive defect in the coatomer (COPI) component epsilon-COP. J Cell Biol 1997; 139(7):1747–59.PubMedCrossRefGoogle Scholar
  137. 137.
    Piguet V, Gu F, Foti M et al. Nef-induced CD4 degradation: A diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes. Cell 1999; 97(l):63–73.PubMedCrossRefGoogle Scholar
  138. 138.
    Valdivia RH, Baggott D, Chuang JS et al. The yeast clathrin adaptor protein complex 1 is required for the efficient retention of a subset of late Golgi membrane proteins. Dev Cell 2002; 2(3):283–94.PubMedCrossRefGoogle Scholar
  139. 139.
    Raiborg C, Bache KG, Gillooly DJ et al. Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes. Nat Cell Biol 2002; 4(5):394–8.PubMedCrossRefGoogle Scholar
  140. 140.
    Sachse M, Urbe S, Oorschot V et al. Bilayered clathrin coats on endosomal vacuoles are involved in protein sorting toward lysosomes. Mol Biol Cell 2002; 13(4):1313–28.PubMedCrossRefGoogle Scholar
  141. 141.
    Kurten RC, Cadena DL, Gill GN. Enhanced degradation of EGF receptors by a sorting nexin, SNX1. Science 1996; 272(5264):1008–10.PubMedCrossRefGoogle Scholar
  142. 142.
    Teasdale RD, Loci D, Houghton F et al. A large family of endosome-localized proteins related to sorting nexin 1. Biochem J 2001; 358(Pt 1):7–16.PubMedCrossRefGoogle Scholar
  143. 143.
    Xu Y, Hortsman H, Seet L et al. SNX3 regulates endosomal function through its PX-domain-mediated interaction with PtdIns(3)P. Nat Cell Biol 2001; 3(7):658–66.PubMedCrossRefGoogle Scholar
  144. 144.
    Ekena K, Stevens TH. The Saccharomyces cerevisiae MVP1 gene interacts with VPS1 and is required for vacuolar protein sorting. Mol Cell Biol 1995; 15(3):1671–8.PubMedGoogle Scholar
  145. 145.
    Voos W, Stevens TH. Retrieval of resident late-Golgi membrane proteins from the prevacuolar compartment of Saccharomyces cerevisiae is dependent on the function of Grdl9p. J Cell Biol 1998; 140(3):577–90.PubMedCrossRefGoogle Scholar
  146. 146.
    Hettema EH, Lewis MJ, Black MW et al. Retromer and the sorting nexins Snx4/4l/42 mediate distinct retrieval pathways from yeast endosomes. EMBO J 2003; 22(3):548–57.PubMedCrossRefGoogle Scholar
  147. 147.
    Haft CR, de la Luz Sierra M, Bafford R et al. Human orthologs of yeast vacuolar protein sorting proteins Vps26, 29, and 35: Assembly into multimeric complexes. Mol Biol Cell 2000; 11(12):4105–16.PubMedGoogle Scholar
  148. 148.
    Haft CR, de la Luz Sierra M, Barr VA et al. Identification of a family of sorting nexin molecules and characterization of their association with receptors. Mol Cell Biol 1998; 18(12):7278–87.PubMedGoogle Scholar
  149. 149.
    Zheng B, Ma YC, Ostrom RS et al. RGS-PX1, a GAP for GalphaS and sorting nexin in vesicular trafficking. Science 2001; 294(5548):1939–42.PubMedCrossRefGoogle Scholar
  150. 150.
    Schapiro FB, Lingwood C, Furuya W et al. pH-independent retrograde targeting of glycolipids to the Golgi complex. Am J Physiol 1998; 274(2 Pt l):C319–32.PubMedGoogle Scholar
  151. 151.
    Falguieres T, Mallard F, Baron C et al. Targeting of Shiga toxin B-subunit to retrograde transport route in association with detergent-resistant membranes. Mol Biol Cell 2001; 12(8):2453–68.PubMedGoogle Scholar
  152. 152.
    Kovbasnjuk O, Edidin M, Donowitz M. Role of lipid rafts in Shiga toxin 1 interaction with the apical surface of Caco-2 cells. J Cell Sci 2001; H4(Pt 22):4025–31.Google Scholar
  153. 153.
    Sievi E, Suntio T, Makarow M. Proteolytic function of GPI-anchored plasma membrane protease Ypslp in the yeast vacuole and Golgi. Traffic 2001; 2(12):896–907.PubMedCrossRefGoogle Scholar
  154. 154.
    Bagnat M, Simons K. Lipid rafts in protein sorting and cell polarity in budding yeast Saccharomyces cerevisiae. Biol Chem 2002; 383(10):1475–80.PubMedCrossRefGoogle Scholar
  155. 155.
    Umebayashi K, Nakano A. Ergosterol is required for targeting of tryptophan permease to the yeast plasma membrane. J Cell Biol 2003; 161(6):1117–31.PubMedCrossRefGoogle Scholar
  156. 156.
    Watanabe R, Funato K, Venkataraman K et al. Sphingolipids are required for the stable membrane association of glycosylphosphatidylinositol-anchored proteins in yeast. J Biol Chem 2002; 277(51):49538–44.PubMedCrossRefGoogle Scholar
  157. 157.
    Munro S. Organelle identity and the targeting of peripheral membrane proteins. Curr Opin Cell Biol 2002; 14(4):506–14.PubMedCrossRefGoogle Scholar
  158. 158.
    Hurley JH, Meyer T. Subcellular targeting by membrane lipids. Curr Opin Cell Biol 2001; 13(2):146–52.PubMedCrossRefGoogle Scholar
  159. 159.
    Levine TP, Munro S. Targeting of golgi-specific pleckstrin homology domains involves both Ptdins 4-Kinase-dependent and-Independent components. Curr Biol 2002; 12(9):695–704.PubMedCrossRefGoogle Scholar
  160. 160.
    Stefan CJ, Audhya A, Emr SD. The yeast synaptojanin-like proteins control the cellular distribution of phosphatidylinositol (4,5)-bisphosphate. Mol Biol Cell 2002; 13(2):542–57.CrossRefGoogle Scholar
  161. 161.
    Bravo J, Karathanassis D, Pacold CM et al. The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate. Mol Cell 2001; 8(4):829–39.PubMedCrossRefGoogle Scholar
  162. 162.
    Simonsen A, Lippe R, Christoforidis S et al. EEA1 links PI(3)K function to Rab5 regulation of endosome fusion. Nature 1998; 394(6692):494–8.PubMedCrossRefGoogle Scholar
  163. 163.
    McBride HM, Rybin V, Murphy C et al. Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13. Cell 1999; 98(3):377–86.CrossRefGoogle Scholar
  164. 164.
    Lippe R, Miaczynska M, Rybin V et al. Functional synergy between Rab5 effector Rabaptin-5 and exchange factor Rabex-5 when physically associated in a complex. Mol Biol Cell 2001; 12(7):2219–28.PubMedGoogle Scholar
  165. 165.
    Christoforidis S, Miaczynska M, Ashman K et al. Phosphatidylinositol-3-OH kinases are Rab5 effectors. Nat Cell Biol 1999; 1(4):249–52.PubMedCrossRefGoogle Scholar
  166. 166.
    Zerial M, McBride H. Rab proteins as membrane organizers. Nat Rev Mol Cell Biol 2001; 2(2):107–17.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  1. 1.Centre for Molecular Medicine and TherapeuticsUniversity of British ColumbiaVancouverCanada
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of British ColumbiaVancouverCanada

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