Clathrin-Mediated Endocytosis

  • Peter S. McPherson
  • Brigitte Ritter
  • Beverly Wendland
Part of the Molecular Biology Intelligence Unit book series (MBIU)


Eukaryotic cells use multiple pathways for the endocytic entry of proteins and lipids at the plasma membrane. To date, the best characterized pathway is clathrin-mediated endocytosis. This chapter presents an overview of the mechanisms of clathrin-mediated endocytosis and how itis regulated. We provide a mechanistic description of how a clathrin-coated vesicle (CCV) is formed, from the stages of initiation to scission to uncoating, as well as address important regulation by protein and lipid kinases and phosphatases. Endocytic events are initiated through the concerted action of the clathrin coat and adaptor proteins that select the transmembrane proteins (cargo) that will be carried into the cell in endocytic vesicles. Accessory proteins and the GTPase dynamin work together with forces provided by actin polymerization to complete the formation of the CCV. The ATPase chaperone Hsc70 and the protein auxilin promote CCV uncoating, a necessary step for the vesicle to fuse with endosomes. The synergistic convergence of powerful experimental strategies such as structural, biochemical and genomic approaches, in vitro assays, and real-time imaging in vivo, have combined to allow the new breakthroughs that are discussed.


Actin Assembly Eps15 Homology Actin Patch Clathrin Coat Endocytic Machinery 
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.
    Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature 2003; 422(6927):37–44.Google Scholar
  2. 2.
    Brodsky FM et al. Biological basket weaving: Formation and function of clathrin-coated vesicles. Annu Rev Cell Dev Biol 2001; 17:517–68.PubMedCrossRefGoogle Scholar
  3. 3.
    McPherson PS, Kay BK, Hussain NK. Signalingon the endocyticpathway. Traffic 2001; 2(6):375–84.PubMedCrossRefGoogle Scholar
  4. 4.
    Rust MJ et al. Assembly of endocytic machinery around individual influenza viruses during viral entry. Nat Struct Mol Biol 2004; 11(6):567–73.PubMedCrossRefGoogle Scholar
  5. 5.
    Sandvig K, van Deurs B. Endocytosis, intracellular transport, and cytotoxic action of Shiga toxin and ricin. Physiol Rev 1996; 76(4):949–66.PubMedGoogle Scholar
  6. 6.
    Robinson MS. Adaptable adaptors for coated vesicles. Trends Cell Biol 2004; 14(4): 167–74.PubMedCrossRefGoogle Scholar
  7. 7.
    Griffiths G etal. The mannose 6-phosphate receptor and the biogenesis of lysosomes. Cell 1988; 52(3):329–41.PubMedCrossRefGoogle Scholar
  8. 8.
    Ludwig T, Le Borgne R, Hoflack B. Roles for mannose-6-phosphate receptors in lysosomal enzyme sorting, IGF-II binding and clathrin-coat assembly. Trends Cell Biol 1995; 5(5):202–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Meyer C et al. mu1A-adaptin-deficient mice:Lethality, loss of AP-1 binding andrerouting of mannose 6-phosphate receptors. EMBO J 2000; 19(10):2193–203.PubMedCrossRefGoogle Scholar
  10. 10.
    Hinners I, Tooze SA. Changing directions: Clathrin-mediated transport between the Golgiand endosomes. J Cell Sci 2003; 116(Pt 5):763–71.PubMedCrossRefGoogle Scholar
  11. 11.
    Austin C, Hinners I, Tooze SA. Direct and GTP-dependent interaction of ADP-ribosylation factor 1 with clathrin adaptor protein AP-1 on immature secretory granules. J Biol Chem 2000; 275(29):21862–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Pearse BM, Bretscher MS. Membrane recycling by coated vesicles. Annu Rev Biochem 1981; 50:85–101.PubMedCrossRefGoogle Scholar
  13. 13.
    Willig KI et al. STED microscopy reveals that synaptotagmin remains clustered after synaptic vesicle exocytosis. Nature 2006; 440(7086):935–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Fernandez-Alfonso T, Kwan R, Ryan TA. Synaptic vesicles interchange their membrane proteins with a large surface reservoir during recycling. Neuron 2006; 51(2): 179–86.PubMedCrossRefGoogle Scholar
  15. 15.
    Murthy VN, De Camilli P. Cell biology of the presynaptic terminal. Annu Rev Neurosci 2003; 26:701–28.PubMedCrossRefGoogle Scholar
  16. 16.
    McNiven MA, Thompson HM. Vesicle formation at the plasma membrane and trans-Golgi network: The same but different. Science 2006; 313(5793):1591–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Wakeham DE et al. Clathrin self-assembly involves coordinated weak interactions favorable for cellular regulation. EMBO J 2003; 22(19):4980–90.PubMedCrossRefGoogle Scholar
  18. 18.
    Fotin A et al. Molecular model for a complete clathrin lattice from electron cryomicroscopy. Nature 2004; 432(7017):573–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Fotin A et al. Structure of an auxilin-bound clathrin coat and its implications for the mechanism of uncoating. Nature 2004; 432(7017):649–53.PubMedCrossRefGoogle Scholar
  20. 20.
    Blondeau F et al. Tandem MS analysis of brain clathrin-coated vesicles reveals their critical involvement in synaptic vesicle recycling. Proc Natl Acad Sci USA 2004; 101(11):3833–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Kirchhausen T, Harrison SC. Protein organization in clathrin trimers. Cell 1981; 23(3):755–61.PubMedCrossRefGoogle Scholar
  22. 22.
    Ungewickell E, Branton D. Assembly units of clathrin coats. Nature 1981; 289(5796):420–2.PubMedCrossRefGoogle Scholar
  23. 23.
    Ungewickell E, Ungewickell H. Bovine brain clathrin light chains impede heavy chain assembly in vitro. J Biol Chem 1991; 266(19): 12710–4.PubMedGoogle Scholar
  24. 24.
    Girard M et al. Non-stoichiometric relationship between clathrin heavy and light chains revealed by quantitative comparative proteomics of clathrin-coated vesicles from brain and liver. Mol Cell Proteomics 2005; 4(8): 1145–54.PubMedCrossRefGoogle Scholar
  25. 25.
    Traub LM. Sorting it out: AP-2 and alternate clathrin adaptors in endocytic cargo selection. J Cell Biol 2003; 163(2):203–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Ritter B et al. Molecular mechanisms in clathrin-mediated membrane budding revealed through subcellular proteomics. Biochem Soc Trans 2004; 32(Pt 5):769–73.PubMedGoogle Scholar
  27. 27.
    Owen DJ, Collins BM, Evans PR. Adaptors for clathrin coats: Structure and function. Annu Rev Cell Dev Biol 2004; 20:153–91.PubMedCrossRefGoogle Scholar
  28. 28.
    Owen DJ et al. The structure and function of the beta 2-adaptin appendage domain. EMBO J 2000; 19(16):4216–27.PubMedCrossRefGoogle Scholar
  29. 29.
    ter Haar E, Harrison SC, Kirchhausen T. Peptide-in-groove interactions link target proteins to the beta-propeller of clathrin. Proc Natl Acad Sci USA 2000; 97(3): 1096–100.PubMedCrossRefGoogle Scholar
  30. 30.
    Schmid EM et al. Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly. PLoS Biol 2006; 4(9):e262.PubMedCrossRefGoogle Scholar
  31. 31.
    Edeling MA et al. Molecular switches involving the AP-2 beta2 appendage regulate endocytic cargo selection and clathrin coat assembly. Dev Cell 2006; 10(3):329–42.PubMedCrossRefGoogle Scholar
  32. 32.
    Knuehl C et al. Novel binding sites on clathrin and adaptors regulate distinct aspects of coat assembly. Traffic 2006; 7(12):1688–700.PubMedCrossRefGoogle Scholar
  33. 33.
    Hinrichsen L et al. Effect of clathrin heavy chain-and alpha-adaptin-specific small inhibitory RNAs on endocytic accessory proteinsand receptor trafficking in HeLa cells. J Biol Chem 2003; 278(46):45160–70.PubMedCrossRefGoogle Scholar
  34. 34.
    Motley A et al. Clathrin-mediated endocytosis in AP-2-depleted cells. J Cell Biol 2003; 162(5):909–18.PubMedCrossRefGoogle Scholar
  35. 35.
    Bonifacino JS, Traub LM. Signals for sorting of transmem brane proteins to endosomes and lysosomes. Annu Rev Biochem 2003;72:395–447.PubMedCrossRefGoogle Scholar
  36. 36.
    Santini F, Keen JH. Endocytosis of activated receptors and clathrin-coated pit formation: Deciphering the chicken or egg relationship. J Cell Biol 1996; 132(6): 1025–36.PubMedCrossRefGoogle Scholar
  37. 37.
    Collins BM et al. Molecular architecture and functional model of the endocytic AP2complex. Cell 2002; 109(4):523–35.PubMedCrossRefGoogle Scholar
  38. 38.
    Gaidarov I, Keen JH. Phosphoinositide-AP-2 interactions required for targeting to plasma membrane clathrin-coated pits. J Cell Biol 1999; l46(4):755–64.CrossRefGoogle Scholar
  39. 39.
    Rohde G, Wenzel D, Haucke V. A phosphatidylinositol (4,5)-bisphosphate binding site within mu2-adaptin regulates clathrin-mediated endocytosis. J Cell Biol 2002; 158(2):209–14.PubMedCrossRefGoogle Scholar
  40. 40.
    Jost M et al. Pnosphatidylinositol-4,5-bisphosphate is required for endocytic coated vesicle formation. Curr Biol 1998; 8(25):1399–402.PubMedCrossRefGoogle Scholar
  41. 41.
    Padron D etal. Phosphatidylinositol phosphate 5-kinase Ibeta recruits AP-2 to the plasma membrane and regulates rates of constitutive endocytosis. J Cell Biol 2003; 162(4):693–701.PubMedCrossRefGoogle Scholar
  42. 42.
    McPherson PS et al. A presynaptic inositol-5-phosphatase. Nature 1996; 379(6563):353–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Cremona O et al. Essential role of phosphoinositide metabolism insynaptic vesicle recycling. Cell 1999; 99(2):179–88.PubMedCrossRefGoogle Scholar
  44. 44.
    Zoncu R et al. Loss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphate. Proc Natl Acad Sci USA 2007;104(10):3793–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Godi A et al. ARF mediates recruitment of PtdIns-4-OH kinase-beta and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex. Nat Cell Biol 1999; 1(5):280–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Krauss M etal. ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidylinositol phosphate kinase type Igamma. J Cell Biol 2003; 162(1):113–24.PubMedCrossRefGoogle Scholar
  47. 47.
    Motley AM et al. Functional analysis of AP-2alpha and mu2 subunits. Mol Biol Cell 2006; 17(12):5298–308.PubMedCrossRefGoogle Scholar
  48. 48.
    Honing S et al. Phosphatidylinositol-(4,5)-bisphosphate regulates sorting signal recognitionby the clathrin-associated adaptor complex AP2. Mol Cell 2005; 18(5):519–31.PubMedCrossRefGoogle Scholar
  49. 49.
    McPherson PS, Ritter B. Peptide motifs: Building the clathrin machinery. Mol Neurobiol 2005; 32(l):73–87.PubMedCrossRefGoogle Scholar
  50. 50.
    Traub LM. Common principles in clathrin-mediated sorting at the Golgi and theplasma membrane. Biochim Biophys Acta 2005; 1744(3):415–37.PubMedCrossRefGoogle Scholar
  51. 51.
    Ehrlich M et al. Endocytosis by random initiation and stabilization of clathrin-coated pits. Cell 2004; 118(5):591–605.PubMedCrossRefGoogle Scholar
  52. 52.
    Owen DJ, Evans PR. A structural explanation for the recognition of tyrosine-based endocytotic signals. Science 1998; 282(5392): 1327–32.PubMedCrossRefGoogle Scholar
  53. 53.
    Eden ER et al. Use of homozygosity mapping to identify a region on chromosome 1 bearing a defective gene that causes autosomal recessive homozygous hypercholesterolemia in two unrelated families. Am J Hum Genet 2001;68(3):653–60.PubMedCrossRefGoogle Scholar
  54. 54.
    Eden ER et al. Restoration of LDL receptor function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1. J Clin Invest 2002; 110(11):1695.PubMedGoogle Scholar
  55. 55.
    Garcia CK et al. Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. Science 2001; 292(5520): 1394–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Chen H et al. Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis. Nature 1998; 394(6695):793–7.PubMedCrossRefGoogle Scholar
  57. 57.
    He G et al. ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2. J Biol Chem 2002; 277(46):44044–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Laporte SA et al. The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis. Proc Natl Acad Sci USA 1999; 96(7):3712–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Legendre-Guillemin V et al. HIP1 and HIP 12 display differential binding to F-actin, AP2, and clathrin: Identification of a novel interaction with clathrin light chain. J Biol Chem 2002; 277(22): 19897–904.PubMedCrossRefGoogle Scholar
  60. 60.
    Metzler M et al. HIP1 functions in clathrin-mediated endocytosis through binding to clathrin and adaptor protein 2. J Biol Chem 2001; 276(42):39271–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Morris SM, Cooper JA. Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2. Traffic 2001; 2(2):111–23.PubMedCrossRefGoogle Scholar
  62. 62.
    Roos J, Kelly RB. Dap 160, a neural-specific Eps15 homology and multiple SH3 domain-containing protein that interacts with Drosophila dynamin. J Biol Chem 1998; 273(30):19108–19.PubMedCrossRefGoogle Scholar
  63. 63.
    Yamabhai M et al. Intersectin, a novel adaptor protein with two Epsl5 homology and five Src homology 3 domains. J Biol Chem 1998; 273(47):31401–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Hussain NK et al. Splice variants of intersectin are components of the endocytic machinery in neurons and non-neuronal cells. J Biol Chem 1999; 274(22):15671–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Gonzalez-Gaitan M, Jackie H. Role of Drosophila alpha-adaptin in presynaptic vesicle recycling. Cell 1997; 88(6):767–76.PubMedCrossRefGoogle Scholar
  66. 66.
    Koh TW, Verstreken P, Bellen HJ. Dap l60/intersectin acts as a stabilizing scaffold required for synaptic development and vesicle endocytosis. Neuron 2004; 43(2):193–205.PubMedCrossRefGoogle Scholar
  67. 67.
    Marie B et al. Dap l60/intersectin scaffolds the periactive zone to achieve high-fidelity endocytosis and normal synaptic growth. Neuron 2004; 43(2):207–19.PubMedCrossRefGoogle Scholar
  68. 68.
    Hussain NK et al. Endocytic protein intersectin-1 regulates actin assembly via Cdc42 and N-WASP. Nat Cell Biol 2001; 3(10):927–32.PubMedCrossRefGoogle Scholar
  69. 69.
    Karnoub AE et al. Molecular basis for Rac1 recognition by guanine nucleotide exchange factors. Nat Struct Biol 2001; 8(12):1037–41.PubMedCrossRefGoogle Scholar
  70. 70.
    Zamanian JL, Kelly RB. Intersectin 1L guanine nucleotide exchange activity is regulated by adjacentsrc homology 3 domains that are also involved in endocytosis. Mol Biol Cell 2003; 14(4):1624–37.PubMedCrossRefGoogle Scholar
  71. 71.
    Engqvist-Goldstein AE, Drubin DG. Actin assembly and endocytosis: From yeast to mammals. Annu Rev Cell Dev Biol 2003; 19:287–332.PubMedCrossRefGoogle Scholar
  72. 72.
    Miliaras NB, Wendland B. EH Proteins: Multivalent regulators of endocytosis (and other pathways). Cell Biochem Biophys 2004;41(2):295–318.PubMedCrossRefGoogle Scholar
  73. 73.
    Duncan MC et al. Yeast Epsl5-like endocytic protein, Pan1p, activates the Arp2/3 complex. Nat Cell Biol 2001; 3(7):687–90.PubMedCrossRefGoogle Scholar
  74. 74.
    Kaksonen M, Toret CP, Drubin DG. A modular design for the clathrin-andactin-mediated endocytosis machinery. Cell 2005; 123(2):305–20.PubMedCrossRefGoogle Scholar
  75. 75.
    Gaidarov I et al. Spatial control of coated-pit dynamics in living cells. Nat Cell Biol 1999; 1(1):1–7.PubMedCrossRefGoogle Scholar
  76. 76.
    Krauss M et al. Stimulation of phosphatidylinositol kinase type I-mediated phosphatidylinositol (4,5)-bisphosphatesynthesis by AP-2mu-cargo complexes. Proc Natl Acad Sci USA 2006; 103(32):11934–9.PubMedCrossRefGoogle Scholar
  77. 77.
    Wasiak S et al. Enthoprotin: A novel clathrin-associated protein identified through subcellular proteomics. J Cell Biol 2002; 158(5):855–62.PubMedCrossRefGoogle Scholar
  78. 78.
    Conner SD, Schroter T, Schmid SL. AAK1-mediated micro2 phosphorylation is stimulated by assembled clathrin. Traffic 2003; 4(12):885–90.PubMedCrossRefGoogle Scholar
  79. 79.
    Jackson AP 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
  80. 80.
    Huang B et al. Identification of novel recognition motifs and regulatory targets for the yeast actin-regulating kinase Prk1p. Mol Biol Cell 2003; 14(12):4871–84.PubMedCrossRefGoogle Scholar
  81. 81.
    Zeng G, Cai M. Regulation of the actin cytoskeleton organization in yeast by a novel serine/ threonine kinase Prk1p. J Cell Biol 1999; l44(1):71–82.CrossRefGoogle Scholar
  82. 82.
    Cope MJ et al. Novel protein kinases Ark1p and Prk1p associate with and regulate the cortical actin cytoskeleton in budding yeast. J Cell Biol 1999; 144(6):1203–18.PubMedCrossRefGoogle Scholar
  83. 83.
    Stefan CJ et al. The phosphoinositide phosphatase Sjl2 is recruited to cortical actin patches in the control of vesicle formation and fission during endocytosis. Mol Cell Biol 2005; 25(8):2910–23.PubMedCrossRefGoogle Scholar
  84. 84.
    Fazi B et al. Unusual binding properties of the SH3 domain of the yeast actin-binding protein Abpl: Structural and functional analysis. J Biol Chem 2002; 277(7):5290–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Conner SD, Schmid SL. CVAK104 is a novel poly-L-lysine-stimulated kinase that targets the beta2-subunit of AP2. J Biol Chem 2005; 280(22):21539–44.PubMedCrossRefGoogle Scholar
  86. 86.
    Duwel M, Ungewickell EJ. Clathrin-dependent association of CVAK104 with endosomes and the trans-Golgi network. Mol Biol Cell 2006; 17(10):4513–25.PubMedCrossRefGoogle Scholar
  87. 87.
    Wilde A et al. EGF receptor signaling stimulates SRC kinase phosphorylation of clathrin, influencing clathrin redistribution and EGF uptake. Cell 1999; 96(5):677–87.PubMedCrossRefGoogle Scholar
  88. 88.
    Slepnev VI et al. Role of phosphorylation in regulation of the assembly of endocytic coat complexes. Science 1998; 281(5378):821–4.PubMedCrossRefGoogle Scholar
  89. 89.
    Cousin MA, Robinson PJ. The dephosphins: Dephosphorylation by calcineurin triggers synaptic vesicle endocytosis. Trends Neurosci 2001; 24(11):659–65.PubMedCrossRefGoogle Scholar
  90. 90.
    Korolchuk VI, Banting G. CK2 and GAK/auxilin2 aremajor protein kinases in clathrin-coated vesicles. Traffic 2002; 3(6):428–39.PubMedCrossRefGoogle Scholar
  91. 91.
    Korolchuk VI, Cozier G, Banting G. Regulation of CK2 activity by phosphatidylinositol phosphates. J Biol Chem 2005; 280(49):40796–801.PubMedCrossRefGoogle Scholar
  92. 92.
    Anggono V et al. Syndapin I is the phosphorylation-regulated dynamin I partner in synaptic vesicle endocytosis. Nat Neurosci 2006; 9(6):752–60.PubMedCrossRefGoogle Scholar
  93. 93.
    Lee SY et al. Regulation of synaptojanin 1 by cyclin-dependent kinase 5 at synapses. Proc Natl Acad Sci USA 2004; 101(2):546–51.PubMedCrossRefGoogle Scholar
  94. 94.
    Tomizawa K et al. Cophosphorylation of amphiphysin I and dynamin I by Cdk5 regulates clathrin-mediated endocytosis of synaptic vesicles. J Cell Biol 2003; 163 (4):813–24.PubMedCrossRefGoogle Scholar
  95. 95.
    Floyd SR et al. Amphiphysin 1 binds the cyclin-dependent kinase (cdk) 5 regulatory subunit p35 and is phosphorylated by cdk5 and cdc2. J Biol Chem 2001; 276(11):8104–10.PubMedCrossRefGoogle Scholar
  96. 96.
    Friesen H et al. Regulation of the yeast amphiphysin homologue Rvs167p by phosphorylation. Mol Biol Cell 2003; 14(7):3027–40.PubMedCrossRefGoogle Scholar
  97. 97.
    Chen H et al. The interaction of epsin and Epsl5 with the clathrin adaptor AP-2 is inhibited by mitotic phosphorylation and enhanced by stimulation-dependent dephosphorylation in nerve terminals. J Biol Chem 1999; 274(6):3257–60.PubMedCrossRefGoogle Scholar
  98. 98.
    Murakami N et al. Phosphorylation of amphiphysin I by minibrain kinase/dual-specificity tyrosine phosphorylation-regulated kinase, a kinase implicated in Down syndrome. J Biol Chem 2006; 281(33):23712–24.PubMedCrossRefGoogle Scholar
  99. 99.
    Chen-Hwang MC et al. Dynamin is a minibrain kinase/dual specificity Yakl-related kinase 1A substrate. J Biol Chem 2002; 277(20): 17597–604.PubMedCrossRefGoogle Scholar
  100. 100.
    Pelkmans L et al. Genome-wide analysis of human kinases in clathrin-and caveolae/raft-mediated endocytosis. Nature 2005; 436(7047):78–86.PubMedCrossRefGoogle Scholar
  101. 101.
    Kaneko T et al. Rho mediates endocytosis of epidermal growth factor receptor through phosphorylation of endophilin Al by Rho-kinase. Genes Cells 2005; 10(10):973–87.PubMedCrossRefGoogle Scholar
  102. 102.
    Chang JS et al. Protein phosphatase-1 binding to scd5p is important for regulation of actin organization and endocytosis in yeast. J Biol Chem 2002; 277(50):48002–8.PubMedCrossRefGoogle Scholar
  103. 103.
    Chang JS et al. Cortical recruitment and nuclear-cytoplasmic shuttling of Scd5p, a protein phosphatase-1-targeting protein involved in actin organization and endocytosis. Mol Biol Cell 2006; 17(1):251–62.PubMedCrossRefGoogle Scholar
  104. 104.
    Sorkin A, Von Zastrow M. Signal transduction and endocytosis: Close encounters of many kinds. Nat Rev Mol Cell Biol 2002; 3(8):600–14.PubMedCrossRefGoogle Scholar
  105. 105.
    Willoughby EA, Collins MK. Dynamic interaction between the dual specificity phosphatase MKP7 and the JNK3 scaffold protein beta-arrestin 2. J Biol Chem 2005; 280(27):25651–8.PubMedCrossRefGoogle Scholar
  106. 106.
    Sterling H et al. Inhibition of protein-tyrosine phosphatase stimulates the dynamin-dependent endocytosis of ROMK1. J Biol Chem 2002; 277(6):4317–23.PubMedCrossRefGoogle Scholar
  107. 107.
    McMahon HT, Gallop JL. Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 2005; 438(7068):590–6.PubMedCrossRefGoogle Scholar
  108. 108.
    Sheetz MP, Singer SJ. Biological membranes as bilayer couples: A molecular mechanism of drug-erythrocyte interactions. Proc Natl Acad Sci USA 1974; 71(11):4457–61.PubMedCrossRefGoogle Scholar
  109. 109.
    Rosenthal JA et al. The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module. J Biol Chem 1999; 274(48):33959–65.PubMedCrossRefGoogle Scholar
  110. 110.
    Kay BK et al. Identification of a novel domain shared by putative components of the endocytic and cytoskeletal machinery. Protein Sci 1999; 8(2):435–8.PubMedGoogle Scholar
  111. 111.
    Hyman J et al. Epsin 1 undergoes nucleocytosolic shuttling and its epsl5 interactor NH(2)-terminal homology (ENTH) domain, structurally similar to Armadillo and HEAT repeats, interacts with the transcription factor promyelocytic leukemia Zn(2)+ finger protein (PLZF). J Cell Biol 2000; 149(3):537–46.PubMedCrossRefGoogle Scholar
  112. 112.
    Ford MG et al. Simultaneous binding of PtdIns(4,5)P2 and clathrin by AP180 in the nucleation of clathrin lattices on membranes. Science 2001; 291(5506): 1051–5.PubMedCrossRefGoogle Scholar
  113. 113.
    Itoh T et al. Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate binding and endocytosis. Science 2001; 291(5506):1047–51.PubMedCrossRefGoogle Scholar
  114. 114.
    Ford MG et al. Curvature of clathrin-coated pits driven by epsin. Nature 2002; 419(6905):361–6.PubMedCrossRefGoogle Scholar
  115. 115.
    Stahelin RV et al. Contrasting membrane interaction mechanisms of AP180 N-terminal homology (ANTH) and epsin N-terminal homology (ENTH) domains. J Biol Chem 2003; 278(31):28993–9.PubMedCrossRefGoogle Scholar
  116. 116.
    Yim YI et al. Exchange of clathrin, AP2 and epsin on clathrin-coated pits in permeabilized tissue culture cells. J Cell Sci 2005; 118(Pt 11):2405–13.PubMedCrossRefGoogle Scholar
  117. 117.
    Hinrichsen L et al. Bending a membrane: How clathrin affects budding. Proc Nad Acad Sci USA 2006; 103(23):8715–20.CrossRefGoogle Scholar
  118. 118.
    Duncan MC, Payne GS. ENTH/ANTH domains expand to the Golgi. Trends Cell Biol 2003; 13(5):211–5.PubMedCrossRefGoogle Scholar
  119. 119.
    Duncan MC, Costaguta G, Payne GS. Yeast epsin-related proteins required for Golgi-endosome traffic define a gamma-adaptin ear-binding motif. Nat Cell Biol 2003; 5(1):77–81.PubMedCrossRefGoogle Scholar
  120. 120.
    Hirst J et al. EpsinR: An ENTH domain-containing protein that interacts with AP-1. Mol Biol Cell 2003; 14(2):625–41.PubMedCrossRefGoogle Scholar
  121. 121.
    Kalthoff C et al. Clint: A novel clathrin-binding ENTH-domain protein at the Golgi. Mol Biol Cell 2002; 13(11):4060–73.PubMedCrossRefGoogle Scholar
  122. 122.
    Mills IG et al. EpsinR: An AP1/clathrin interacting protein involved in vesicle trafficking. J Cell Biol 2003; 160(2):213–22.PubMedCrossRefGoogle Scholar
  123. 123.
    Bielli A et al. Regulation of Sar1 NH2 terminus by GTP binding and hydrolysis promotes membrane deformation to control COPII vesicle fission. J Cell Biol 2005; 171(6):919–24.PubMedCrossRefGoogle Scholar
  124. 124.
    Lee MC et al. Sar1p N-terminal helix initiates membrane curvature and completes the fission of a COPII vesicle. Cell 2005; 122(4):605–17.PubMedCrossRefGoogle Scholar
  125. 125.
    Huang M et al. Crystal structure of Sar1-GDP at 1.7 A resolution and the role of the NH2 terminus in ER export. J Cell Biol 2001; 155(6):937–48.PubMedCrossRefGoogle Scholar
  126. 126.
    Bi X, Corpina RA, Goldberg J. Structure of the Sec23/24-Sar1 prebudding complex of the COPII vesicle coat. Nature 2002; 419(6904):271–7.PubMedCrossRefGoogle Scholar
  127. 127.
    David C, Solimena M, De Camilli P. Autoimmunity in stiff-Man syndrome with breast cancer is targeted to the C-terminal region of human amphiphysin, a protein similar to the yeast proteins, Rvs167 and Rvs161. FEBS Lett 1994; 351(1):73–9.PubMedCrossRefGoogle Scholar
  128. 128.
    Ramjaun AR et al. Identification and characterization of a nerve terminal-enriched amphiphysin isoform. J Biol Chem 1997; 272(26):16700–6.PubMedCrossRefGoogle Scholar
  129. 129.
    Sakamuro D et al. BIN1 is a novel MYC-interacting protein with features of a tumour suppressor. Nat Genet 1996; 14(1):69–77.PubMedCrossRefGoogle Scholar
  130. 130.
    Ramjaun AR et al. The N terminus of amphiphysin II mediates dimerization and plasma membrane targeting. J Biol Chem 1999; 274(28):19785–91.PubMedCrossRefGoogle Scholar
  131. 131.
    Wigge P et al. Amphiphysin heterodimers: Potential role in clathrin-mediated endocytosis. Mol Biol Cell 1997; 8(10):2003–15.PubMedGoogle Scholar
  132. 132.
    Takei K et al. Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis. Nat Cell Biol 1999; 1(1):33–9.PubMedCrossRefGoogle Scholar
  133. 133.
    Peter BJ et al. BAR domains as sensors of membrane curvature: The amphiphysin BAR structure. Science 2004; 303(5657):495–9.PubMedCrossRefGoogle Scholar
  134. 134.
    de Heuvel E et al. Identification of the major synaptojanin-binding proteins in brain. J Biol Chem 1997; 272(13):8710–16.PubMedCrossRefGoogle Scholar
  135. 135.
    Ringstad N, Nemoto Y, De Camilli P. The SH3p4/Sh3p8/SH3pl3 protein family: Binding partners for synaptojanin and dynamin via a Grb2-like Src homology 3 domain. Proc Natl Acad Sci USA 1997; 94(16):8569–74.PubMedCrossRefGoogle Scholar
  136. 136.
    Gallop JL et al. Mechanism of endophilin N-BAR domain-mediated membrane curvature. EMBO J 2006; 25(12):2898–910.PubMedCrossRefGoogle Scholar
  137. 137.
    Masuda M et al. Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms. EMBO J 2006; 25(12):2889–97.PubMedCrossRefGoogle Scholar
  138. 138.
    Weissenhorn W. Crystal structure of the endophilin-A1 BAR domain. J Mol Biol 2005; 351(3):653–61.PubMedCrossRefGoogle Scholar
  139. 139.
    Farsad K et al. Generation of high curvature membranes mediated by direct endophilin bilayer interactions. J Cell Biol 2001; 155(2):193–200.PubMedCrossRefGoogle Scholar
  140. 140.
    Gallop JL, Butler PJ, McMahon HT. Endophilin and CtBP/BARS are not acyl transferases in endocytosis or Golgi fission. Nature 2005; 438(7068):675–8.PubMedCrossRefGoogle Scholar
  141. 141.
    Itoh T et al. Dynamin and the actin cytoskeleton cooperatively regulate plasma membrane invagination by BAR and F-BAR proteins. Dev Cell 2005; 9(6):791–804.PubMedCrossRefGoogle Scholar
  142. 142.
    Tsujita K et al. Coordination between the actin cytoskeleton and membrane deformation by a novel membrane tubulation domain of PCH proteins is involved in endocytosis. J Cell Biol 2006; 172(2):269–79.PubMedCrossRefGoogle Scholar
  143. 143.
    Modregger J et al. All three PACSIN isoforms bind to endocytic proteins and inhibit endocytosis. J Cell Sci 2000; 113(Pt 24):4511–21.PubMedGoogle Scholar
  144. 144.
    Qualmann B et al. Syndapin I, a synaptic dynamin-binding protein that associates with the neural Wiskott-Aldrich syndrome protein. Mol Biol Cell 1999; 10(2):501–13.PubMedGoogle Scholar
  145. 145.
    Salim K et al. Distinct specificity in the recognition of phosphoinositides by the pleckstrin homology domains of dynamin and Bruton’s tyrosine kinase. EMBO J 1996; 15(22):6241–50.PubMedGoogle Scholar
  146. 146.
    Sever S, Muhlberg AB, Schmid SL. Impairment of dynamin’s GAP domain stimulates receptor-mediated endocytosis. Nature 1999; 398(6727):481–6.PubMedCrossRefGoogle Scholar
  147. 147.
    Gout I et al. The GTPase dynamin binds to and is activated by a subset of SH3 domains. Cell 1993; 75(1):25–36.PubMedGoogle Scholar
  148. 148.
    van der Bliek AM, Meyerowitz EM. Dynamin-like protein encoded by the Drosophila shibire gene associated with vesicular traffic. Nature 1991; 351(6325):411–4.PubMedCrossRefGoogle Scholar
  149. 149.
    Kosaka T, Ikeda K. Possible temperature-dependent blockage of synaptic vesicle recycling induced by a single gene mutation in Drosophila. J Neurobiol 1983; 14(3):207–25.PubMedCrossRefGoogle Scholar
  150. 150.
    Hinshaw JE, Schmid SL. Dynamin self-assembles into rings suggesting a mechanism for coated vesicle budding. Nature 1995; 374(6518):190–2.PubMedCrossRefGoogle Scholar
  151. 151.
    Takei K et al. Tubular membrane invaginations coated by dynamin rings are induced by GTP-gamma S in nerve terminals. Nature 1995; 374(6518):186–90.PubMedCrossRefGoogle Scholar
  152. 152.
    Stowell MH et al. Nucleotide-dependent conformational changes in dynamin: Evidence for a mechanochemical molecular spring. Nat Cell Biol 1999; 1(1):27–32.PubMedCrossRefGoogle Scholar
  153. 153.
    Roux A et al. GTP-dependent twisting of dynamin implicates constriction and tension in membrane fission. Nature 2006; 441(7092):528–31.PubMedCrossRefGoogle Scholar
  154. 154.
    Kirchhausen T. Clathrin. Annu Rev Biochem 2000; 69:699–727.PubMedCrossRefGoogle Scholar
  155. 155.
    Lee DW et al. Recruitment dynamics of GAK and auxilin to clathrin-coated pits during endocytosis. J Cell Sci 2006; 119(Pt 17):3502–12.PubMedCrossRefGoogle Scholar
  156. 156.
    Massol RH et al. A burst of auxilin recruitment determines the onset of clathrin-coated vesicle uncoating. Proc Natl Acad Sci USA 2006; 103(27):10265–70.PubMedCrossRefGoogle Scholar
  157. 157.
    Leshchyns’ka I et al. The adhesion molecule CHL1 regulates uncoating of clathrin-coated synaptic vesicles. Neuron 2006; 52(6):1011–25.CrossRefGoogle Scholar
  158. 158.
    McNiven MA et al. Regulated interactions between dynamin and the actin-binding protein cortactin modulate cell shape. J Cell Biol 2000; 151(1):187–98.PubMedCrossRefGoogle Scholar
  159. 159.
    Merrifield CJ et al. Imaging actin and dynamin recruitment during invagination of single clathrin-coated pits. Nat Cell Biol 2002; 4(9):691–8.PubMedCrossRefGoogle Scholar
  160. 160.
    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
  161. 161.
    Yarar D, Waterman-Storer CM, Schmid SL. A dynamic actin cytoskeleton functions at multiple stages of clathrin-mediated endocytosis. Mol Biol Cell 2005; 16(2):964–75.PubMedCrossRefGoogle Scholar
  162. 162.
    Gottlieb TA et al. Actin microfilaments play a critical role in endocytosis at the apical but not the basolateral surface of polarized epithelial cells. J Cell Biol 1993; 120(3):695–710.PubMedCrossRefGoogle Scholar
  163. 163.
    Kubler E, Riezman H. Actin and fimbrin are required for the internalization step of endocytosis in yeast. EMBO J 1993; 12(7):2855–62.PubMedGoogle Scholar
  164. 164.
    Warren DT et al. Sla1p couples the yeast endocytic machinery to proteins regulating actin dynamics. J Cell Sci 2002; 115(Pt 8):1703–15.PubMedGoogle Scholar
  165. 165.
    Kaksonen M, Sun Y, Drubin DG. A pathway for association of receptors, adaptors, and actin during endocytic internalization. Cell 2003; 115(4):475–87.PubMedCrossRefGoogle Scholar
  166. 166.
    Moreau V et al. The yeast actin-related protein Arp2p is required for the internalization step of endocytosis. Mol Biol Cell 1997; 8(7):1361–75.PubMedGoogle Scholar
  167. 167.
    Wen KK, Rubenstein PA. Acceleration of yeast actin polymerization by yeast Arp2/3 complex does not require an Arp2/3-activating protein. J Biol Chem 2005; 280(25):24168–74.PubMedCrossRefGoogle Scholar
  168. 168.
    Kaksonen M, Toret CP, Drubin DG. Harnessing actin dynamics for clathrin-mediated endocytosis. Nat Rev Mol Cell Biol 2006; 7(6):404–14.PubMedCrossRefGoogle Scholar
  169. 169.
    Rodal AA et al. Negative regulation of yeast WASp by two SH3 domain-containing proteins. Curr Biol 2003; 13(12): 1000–8.PubMedCrossRefGoogle Scholar
  170. 170.
    Toshima J et al. Phosphoregulation of Arp2/3-dependent actin assembly during receptor-mediated endocytosis. Nat Cell Biol 2005; 7(3):246–54.PubMedCrossRefGoogle Scholar
  171. 171.
    Jonsdottir GA, Li R. Dynamics of yeast Myosin I: Evidence for a possible role in scission of endocytic vesicles. Curr Biol 2004; 14(17):1604–9.PubMedCrossRefGoogle Scholar
  172. 172.
    Sun Y, Martin AC, Drubin DG. Endocytic internalization in budding yeast requires coordinated actin nucleation and myosin motor activity. Dev Cell 2006; 11(1):33–46.PubMedCrossRefGoogle Scholar
  173. 173.
    D’Agostino JL, Goode BL. Dissection of Arp2/3 complex actin nucleation mechanism and distinct roles for its nucleation-promoting factors in Saccharomyces cerevisiae. Genetics 2005; 171(1):35–47.PubMedCrossRefGoogle Scholar
  174. 174.
    Holtzman DA, Yang S, Drubin DG. Synthetic-lethal interactions identify two novel genes, SLA1 and SLA2, that control membrane cytoskeleton assembly in Saccharomyces cerevisiae. J Cell Biol 1993; 122(3):635–44.PubMedCrossRefGoogle Scholar
  175. 175.
    Raths S et al. End3 and end4: Two mutants defective in receptor-mediated and fluid-phase endocytosis in Saccharomyces cerevisiae. J Cell Biol 1993; 120(1):55–65.PubMedCrossRefGoogle Scholar
  176. 176.
    Kalchman MA et al. HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain. Nat Genet 1997; 16(1):44–53.PubMedCrossRefGoogle Scholar
  177. 177.
    Engqvist-Goldstein AE et al. The actin-binding protein HiplR associates with clathrin during early stages of endocytosis and promotes clathrin assembly in vitro. J Cell Biol 2001; 154(6): 1209–23.PubMedCrossRefGoogle Scholar
  178. 178.
    Wesp A et al. End4p/Sla2p interacts with actin-associated proteins for endocytosis in Saccharomyces cerevisiae. Mol Biol Cell 1997; 8(11):2291–306.PubMedGoogle Scholar
  179. 179.
    Huh WK et al. Global analysis of protein localization in budding yeast. Nature 2003; 425(6959):686–91.PubMedCrossRefGoogle Scholar
  180. 180.
    Stepp JD et al. A late Golgi sorting function for Saccharomyces cerevisiae Apm1p, but not for Apm2p, a second yeast clathrin AP medium chain-related protein. Mol Biol Cell 1995; 6(1):41–58.PubMedGoogle Scholar
  181. 181.
    Huang KM 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
  182. 182.
    Yeung BG, Phan HL, Payne GS. Adaptor complex-independent clathrin function in yeast. Mol Biol Cell 1999; 10(11):3643–59.PubMedGoogle Scholar
  183. 183.
    Vater CA et al. The VPS1 protein, a homolog of dynamin required for vacuolar protein sorting in Saccharomyces cerevisiae, is a GTPase with two functionally separable domains. J Cell Biol 1992; 119(4):773–86.PubMedCrossRefGoogle Scholar
  184. 184.
    Yu X, Cai M. The yeast dynamin-related GTPase Vpslp functions in the organization of the actin cytoskeleton via interaction with Slalp. J Cell Sci 2004; 117(Pt 17):3839–53.PubMedCrossRefGoogle Scholar
  185. 185.
    Fujimoto LM et al. Actin assembly plays a variable, but not obligatory role in receptor-mediated endocytosis in mammalian cells. Traffic 2000; 1(2): 161–71.PubMedCrossRefGoogle Scholar
  186. 186.
    Lamaze C et al. The actin cytoskeleton is required for receptor-mediated endocytosis in mammalian cells. J Biol Chem 1997; 272(33):20332–5.PubMedCrossRefGoogle Scholar
  187. 187.
    Moseley JB, Goode BL. The yeast actin cytoskeleton: From cellular function to biochemical mechanism. Microbiol Mol Biol Rev 2006; 70(3):605–45.PubMedCrossRefGoogle Scholar
  188. 188.
    Smythe E, Ayscough KR. Actin regulation in endocytosis. J Cell Sci 2006; 119(Pt 22):4589–4598.PubMedCrossRefGoogle Scholar
  189. 189.
    Buss F et al. Myosin VI isoform localized to clathrin-coated vesicles with a role in clathrin-mediated endocytosis. EMBO J 2001; 20(14):3676–84.PubMedCrossRefGoogle Scholar
  190. 190.
    Hasson T. Myosin VI: Two distinct roles in endocytosis. J Cell Sci 2003; H6(Pt 17):3453–61.CrossRefGoogle Scholar
  191. 191.
    Taunton J. Actin filament nucleation by endosomes, lysosomes and secretory vesicles. Curr Opin Cell Biol 2001; 13(1):85–91.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  • Peter S. McPherson
    • 2
  • Brigitte Ritter
    • 2
  • Beverly Wendland
    • 1
  1. 1.Department of BiologyThe Johns Hopkins UniversityBaltimoreUSA
  2. 2.Department of Neurology and Neurosurgery Montreal Neurological InstituteMcGill UniversityMontrealCanada

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