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Hijacking the endocytic machinery by microbial pathogens

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Abstract

Understanding the mechanisms that microbes exploit to invade host cells and cause disease is crucial if we are to eliminate their threat. Although pathogens use a variety of microbial factors to trigger entry into non-phagocytic cells, their targeting of the host cell process of endocytosis has emerged as a common theme. To accomplish this, microbes often rewire the normal course of particle internalization, frequently usurping theoretical maximal sizes to permit entry and reconfiguring molecular components that were once thought to be required for vesicle formation. Here, we discuss recent advances in our understanding of how toxins, viruses, bacteria, and fungi manipulate the host cell endocytic machinery to generate diseases. Additionally, we will reveal the advantages of using these organisms to expand our general knowledge of endocytic mechanisms in eukaryotic cells.

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Abbreviations

AP-2:

Adaptor protein-2

ASFV:

African swine fever virus

BPV:

Bovine papillomavirus

Cav-1:

Caveolin-1

CCP:

Clathrin-coated pit

CCV:

Clathrin-coated vesicle

CD2AP:

CD2-associated protein

CME:

Clathrin-mediated endocytosis

CMG:

Capillary morphogenesis

CT:

Cholera toxin

Dab2:

Disabled-2

DRM:

Detergent-resistant motif

EBVO:

Ebola virus

EGFR:

Epidermal growth factor receptor

EPEC:

Enteropathogenic Escherichia coli

Eps15:

Epidermal growth factor protein substrate 15

epsin:

Eps15 interaction protein

GPI-AP:

Glycosylphosphatidylinositol-anchored proteins

GFP:

Green fluorescent protein

GPCR:

G protein-coupled receptor

HCV:

Hepatitis C virus

HEGEC:

Human endometrial gland epithelial cell

HIV:

Human immunodeficiency virus

KSHV:

Kaposi's sarcoma-associated herpesvirus

LDLR:

Low-density lipoprotein receptor

MβCD:

Methyl-β-cyclodextran

MDC:

Monodansylcadaverine

MEFs:

Mouse embryonic fibroblasts

PA7mer:

Heptameric PA

PV:

Poliovirus

PtdIns(4,5)P2 :

Phosphatidylinositol (4,5) bisphosphate

RNAi:

Ribonucleic acid interference

siRNA:

Small interfering RNA

TEM:

Tumor endothelial marker

UIM:

Ubiquitin interacting motif

UPEC:

Uropathogenic Escherichia coli

References

  • Abrami L, Liu S, Cosson P, Leppla SH, van der Goot FG (2003) Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process. J Cell Biol 160:321–328

    Article  CAS  PubMed  Google Scholar 

  • Abrami L, Kunz B, van der Goot FG (2010a) Anthrax toxin triggers the activation of src-like kinases to mediate its own uptake. Proc Natl Acad Sci U S A 107:1420–1424

    Article  CAS  PubMed  Google Scholar 

  • Abrami L, Bischofberger M, Kunz B, Groux R, van der Goot FG (2010b) Endocytosis of the anthrax toxin is mediated by clathrin, actin and unconventional adaptors. PLoS Pathog 6:e1000792

    Article  PubMed  CAS  Google Scholar 

  • Acosta EG, Castilla V, Damonte EB (2009) Alternative infectious entry pathways for dengue virus serotypes into mammalian cells. Cell Microbiol 11:1533–1549

    Article  CAS  PubMed  Google Scholar 

  • Anderson HA, Chen Y, Norkin LC (1996) Bound simian virus 40 translocates to caveolin-enriched membrane domains, and its entry is inhibited by drugs that selectively disrupt caveolae. Mol Biol Cell 7:1825–1834

    CAS  PubMed  Google Scholar 

  • Bajmoczi M, Gadjeva M, Alper SL, Pier GB, Golan DE (2009) Cystic fibrosis transmembrane conductance regulator and caveolin-1 regulate epithelial cell internalization of Pseudomonas aeruginosa. Am J Physiol Cell Physiol 297:C263–C277

    Article  CAS  PubMed  Google Scholar 

  • Baorto DM, Gao Z, Malaviya R, Dustin ML, van der Merwe A, Lublin DM, Abraham SN (1997) Survival of FimH-expressing enterobacteria in macrophages relies on glycolipid traffic. Nature 389:636–639

    Article  CAS  PubMed  Google Scholar 

  • Bashkirov PV, Akimov SA, Evseev AI, Schmid SL, Zimmerberg J, Frolov VA (2008) GTPase cycle of dynamin is coupled to membrane squeeze and release, leading to spontaneous fission. Cell 135:1276–1286

    Article  CAS  PubMed  Google Scholar 

  • Benmerah A, Bayrou M, Cerf-Bensussan N, Dautry-Varsat A (1999) Inhibition of clathrin-coated pit assembly by an Eps15 mutant. J Cell Sci 112(Pt 9):1303–1311

    CAS  PubMed  Google Scholar 

  • Benmerah A, Poupon V, Cerf-Bensussan N, Dautry-Varsat A (2000) Mapping of Eps15 domains involved in its targeting to clathrin-coated pits. J Biol Chem 275:3288–3295

    Article  CAS  PubMed  Google Scholar 

  • Bhattacharyya S, Warfield KL, Ruthel G, Bavari S, Aman MJ, Hope TJ (2010) Ebola virus uses clathrin-mediated endocytosis as an entry pathway. Virology 401:18–28

    Article  CAS  PubMed  Google Scholar 

  • Biswas D, Niwa H, Itoh K (2004) Infection with Campylobacter jejuni induces tyrosine-phosphorylated proteins into INT-407 cells. Microbiol Immunol 48:221–228

    CAS  PubMed  Google Scholar 

  • Blanchard E, Belouzard S, Goueslain L, Wakita T, Dubuisson J, Wychowski C, Rouille Y (2006) Hepatitis C virus entry depends on clathrin-mediated endocytosis. J Virol 80:6964–6972

    Article  CAS  PubMed  Google Scholar 

  • Boleti H, Benmerah A, Ojcius DM, Cerf-Bensussan N, Dautry-Varsat A (1999) Chlamydia infection of epithelial cells expressing dynamin and Eps15 mutants: clathrin-independent entry into cells and dynamin-dependent productive growth. J Cell Sci 112(Pt 10):1487–1496

    CAS  PubMed  Google Scholar 

  • Bonazzi M, Veiga E, Pizarro-Cerda J, Cossart P (2008) Successive post-translational modifications of E-cadherin are required for InlA-mediated internalization of Listeria monocytogenes. Cell Microbiol 10:2208–2222

    Article  CAS  PubMed  Google Scholar 

  • Bousarghin L, Touze A, Sizaret PY, Coursaget P (2003) Human papillomavirus types 16, 31, and 58 use different endocytosis pathways to enter cells. J Virol 77:3846–3850

    Article  CAS  PubMed  Google Scholar 

  • Brandenburg B, Lee LY, Lakadamyali M, Rust MJ, Zhuang X, Hogle JM (2007) Imaging poliovirus entry in live cells. PLoS Biol 5:e183

    Article  PubMed  CAS  Google Scholar 

  • Brodsky FM, Chen CY, Knuehl C, Towler MC, Wakeham DE (2001) Biological basket weaving: formation and function of clathrin-coated vesicles. Annu Rev Cell Dev Biol 17:517–568

    Article  CAS  PubMed  Google Scholar 

  • Broeck DV, Lagrou AR, De Wolf MJ (2007) Distinct role of clathrin-mediated endocytosis in the functional uptake of cholera toxin. Acta Biochim Pol 54:757–767

    PubMed  Google Scholar 

  • Byrne CM, Clyne M, Bourke B (2007) Campylobacter jejuni adhere to and invade chicken intestinal epithelial cells in vitro. Microbiology 153:561–569

    Article  CAS  PubMed  Google Scholar 

  • Carbone R, Fre S, Iannolo G, Belleudi F, Mancini P, Pelicci PG et al (1997) eps15 and eps15R are essential components of the endocytic pathway. Cancer Res 57:5498–5504

    CAS  PubMed  Google Scholar 

  • Chen Y, Thelin WR, Yang B, Milgram SL, Jacobson K (2006) Transient anchorage of cross-linked glycosyl-phosphatidylinositol-anchored proteins depends on cholesterol, Src family kinases, caveolin, and phosphoinositides. J Cell Biol 175:169–178

    Article  CAS  PubMed  Google Scholar 

  • Cheng ZJ, Singh RD, Wang TK, Holicky EL, Wheatley CL, Bernlohr DA et al (2010) Stimulation of GLUT4 (glucose transporter isoform 4) storage vesicle formation by sphingolipid depletion. Biochem J 427:143–150

    Article  CAS  PubMed  Google Scholar 

  • Coller KE, Berger KL, Heaton NS, Cooper JD, Yoon R, Randall G (2009) RNA interference and single particle tracking analysis of hepatitis C virus endocytosis. PLoS Pathog 5:e1000702

    Article  PubMed  CAS  Google Scholar 

  • Conner SD, Schmid SL (2003) Regulated portals of entry into the cell. Nature 422:37–44

    Article  CAS  PubMed  Google Scholar 

  • Cossart P, Sansonetti PJ (2004) Bacterial invasion: the paradigms of enteroinvasive pathogens. Science 304:242–248

    Article  CAS  PubMed  Google Scholar 

  • Damke H, Baba T, van der Bliek AM, Schmid SL (1995) Clathrin-independent pinocytosis is induced in cells overexpressing a temperature-sensitive mutant of dynamin. J Cell Biol 131:69–80

    Article  CAS  PubMed  Google Scholar 

  • Damm EM, Pelkmans L, Kartenbeck J, Mezzacasa A, Kurzchalia T, Helenius A (2005) Clathrin- and caveolin-1-independent endocytosis: entry of simian virus 40 into cells devoid of caveolae. J Cell Biol 168:477–488

    Article  CAS  PubMed  Google Scholar 

  • Danthi P, Chow M (2004) Cholesterol removal by methyl-beta-cyclodextrin inhibits poliovirus entry. J Virol 78:33–41

    Article  CAS  PubMed  Google Scholar 

  • Day PM, Lowy DR, Schiller JT (2003) Papillomaviruses infect cells via a clathrin-dependent pathway. Virology 307:1–11

    Article  CAS  PubMed  Google Scholar 

  • De Haan L, Hirst TR (2004) Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms (review). Mol Membr Biol 21:77–92

    Article  PubMed  CAS  Google Scholar 

  • Deinhardt K, Berninghausen O, Willison HJ, Hopkins CR, Schiavo G (2006) Tetanus toxin is internalized by a sequential clathrin-dependent mechanism initiated within lipid microdomains and independent of epsin1. J Cell Biol 174:459–471

    Article  CAS  PubMed  Google Scholar 

  • del Pozo MA, Balasubramanian N, Alderson NB, Kiosses WB, Grande-Garcia A, Anderson RG, Schwartz MA (2005) Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization. Nat Cell Biol 7:901–908

    Article  PubMed  CAS  Google Scholar 

  • DeTulleo L, Kirchhausen T (1998) The clathrin endocytic pathway in viral infection. EMBO J 17:4585–4593

    Article  CAS  PubMed  Google Scholar 

  • Di Fiore PP, De Camilli P (2001) Endocytosis and signaling. an inseparable partnership. Cell 106:1–4

    Article  PubMed  Google Scholar 

  • Doherty GJ, McMahon HT (2009) Mechanisms of endocytosis. Annu Rev Biochem 78:857–902

    Article  CAS  PubMed  Google Scholar 

  • Dokainish H, Gavicherla B, Shen Y, Ireton K (2007) The carboxyl-terminal SH3 domain of the mammalian adaptor CrkII promotes internalization of Listeria monocytogenes through activation of host phosphoinositide 3-kinase. Cell Microbiol 9:2497–2516

    Article  CAS  PubMed  Google Scholar 

  • Duncan MJ, Shin JS, Abraham SN (2002) Microbial entry through caveolae: variations on a theme. Cell Microbiol 4:783–791

    Article  CAS  PubMed  Google Scholar 

  • Duncan L, Yoshioka M, Chandad F, Grenier D (2004) Loss of lipopolysaccharide receptor CD14 from the surface of human macrophage-like cells mediated by Porphyromonas gingivalis outer membrane vesicles. Microb Pathog 36:319–325

    Article  CAS  PubMed  Google Scholar 

  • Echarri A, Del Pozo MA (2006) Caveolae internalization regulates integrin-dependent signaling pathways. Cell Cycle 5:2179–2182

    CAS  PubMed  Google Scholar 

  • Edeling MA, Smith C, Owen D (2006) Life of a clathrin coat: insights from clathrin and AP structures. Nat Rev Mol Cell Biol 7:32–44

    Article  CAS  PubMed  Google Scholar 

  • Ellington JK, Reilly SS, Ramp WK, Smeltzer MS, Kellam JF, Hudson MC (1999) Mechanisms of Staphylococcus aureus invasion of cultured osteoblasts. Microb Pathog 26:317–323

    Article  CAS  PubMed  Google Scholar 

  • Eto DS, Gordon HB, Dhakal BK, Jones TA, Mulvey MA (2008) Clathrin, AP-2, and the NPXY-binding subset of alternate endocytic adaptors facilitate FimH-mediated bacterial invasion of host cells. Cell Microbiol 10:2553–2567

    Article  CAS  PubMed  Google Scholar 

  • Evans MJ, von Hahn T, Tscherne DM, Syder AJ, Panis M, Wolk B et al (2007) Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 446:801–805

    Article  CAS  PubMed  Google Scholar 

  • Ewers H, Romer W, Smith AE, Bacia K, Dmitrieff S, Chai W et al (2010) GM1 structure determines SV40-induced membrane invagination and infection. Nat Cell Biol 12:11–18, sup pp 11-12

    Article  CAS  PubMed  Google Scholar 

  • Fishman PH, Orlandi PA (2003) Cholera toxin internalization and intoxication. J Cell Sci 116:431–432, author reply 432-433

    Article  PubMed  Google Scholar 

  • Frick M, Bright NA, Riento K, Bray A, Merrified C, Nichols BJ (2007) Coassembly of flotillins induces formation of membrane microdomains, membrane curvature, and vesicle budding. Curr Biol 17:1151–1156

    Article  CAS  PubMed  Google Scholar 

  • Glebov OO, Bright NA, Nichols BJ (2006) Flotillin-1 defines a clathrin-independent endocytic pathway in mammalian cells. Nat Cell Biol 8:46–54

    Article  CAS  PubMed  Google Scholar 

  • Goosney DL, DeVinney R, Finlay BB (2001) Recruitment of cytoskeletal and signaling proteins to enteropathogenic and enterohemorrhagic Escherichia coli pedestals. Infect Immun 69:3315–3322

    Article  CAS  PubMed  Google Scholar 

  • Grassme H, Jendrossek V, Riehle A, von Kurthy G, Berger J, Schwarz H et al (2003) Host defense against Pseudomonas aeruginosa requires ceramide-rich membrane rafts. Nat Med 9:322–330

    Article  CAS  PubMed  Google Scholar 

  • Greene W, Gao SJ (2009) Actin dynamics regulate multiple endosomal steps during Kaposi’s sarcoma-associated herpesvirus entry and trafficking in endothelial cells. PLoS Pathog 5:e1000512

    Article  PubMed  CAS  Google Scholar 

  • Gruenberg J, van der Goot FG (2006) Mechanisms of pathogen entry through the endosomal compartments. Nat Rev Mol Cell Biol 7:495–504

    Article  CAS  PubMed  Google Scholar 

  • Haglund K, Di Fiore PP, Dikic I (2003) Distinct monoubiquitin signals in receptor endocytosis. Trends Biochem Sci 28:598–603

    Article  CAS  PubMed  Google Scholar 

  • Hansen CG, Nichols BJ (2009) Molecular mechanisms of clathrin-independent endocytosis. J Cell Sci 122:1713–1721

    Article  CAS  PubMed  Google Scholar 

  • Harder T, Simons K (1997) Caveolae, DIGs, and the dynamics of sphingolipid-cholesterol microdomains. Curr Opin Cell Biol 9:534–542

    Article  CAS  PubMed  Google Scholar 

  • Harris HJ, Farquhar MJ, Mee CJ, Davis C, Reynolds GM, Jennings A et al (2008) CD81 and claudin 1 coreceptor association: role in hepatitis C virus entry. J Virol 82:5007–5020

    Article  CAS  PubMed  Google Scholar 

  • Harvey HA, Jennings MP, Campbell CA, Williams R, Apicella MA (2001) Receptor-mediated endocytosis of Neisseria gonorrhoeae into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor. Mol Microbiol 42:659–672

    Article  CAS  PubMed  Google Scholar 

  • Henkel JS, Baldwin MR, Barbieri JT (2010) Toxins from bacteria. EXS 100:1–29

    PubMed  Google Scholar 

  • Henley JR, Krueger EW, Oswald BJ, McNiven MA (1998) Dynamin-mediated internalization of caveolae. J Cell Biol 141:85–99

    Article  CAS  PubMed  Google Scholar 

  • Hernaez B, Alonso C (2010) Dynamin- and clathrin-dependent endocytosis in African swine fever virus entry. J Virol 84:2100–2109

    Article  CAS  PubMed  Google Scholar 

  • Heuser JE, Anderson RG (1989) Hypertonic media inhibit receptor-mediated endocytosis by blocking clathrin-coated pit formation. J Cell Biol 108:389–400

    Article  CAS  PubMed  Google Scholar 

  • Hicke L, Dunn R (2003) Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. Annu Rev Cell Dev Biol 19:141–172

    Article  CAS  PubMed  Google Scholar 

  • Hindmarsh PL, Laimins LA (2007) Mechanisms regulating expression of the HPV 31 L1 and L2 capsid proteins and pseudovirion entry. Virol J 4:19

    Article  PubMed  CAS  Google Scholar 

  • Hodinka RL, Davis CH, Choong J, Wyrick PB (1988) Ultrastructural study of endocytosis of Chlamydia trachomatis by McCoy cells. Infect Immun 56:1456–1463

    CAS  PubMed  Google Scholar 

  • Hu L, McDaniel JP, Kopecko DJ (2006) Signal transduction events involved in human epithelial cell invasion by Campylobacter jejuni 81-176. Microb Pathog 40:91–100

    Article  CAS  PubMed  Google Scholar 

  • Hybiske K, Stephens RS (2007) Mechanisms of Chlamydia trachomatis entry into nonphagocytic cells. Infect Immun 75:3925–3934

    Article  CAS  PubMed  Google Scholar 

  • Jonquieres R, Pizarro-Cerda J, Cossart P (2001) Synergy between the N- and C-terminal domains of InlB for efficient invasion of non-phagocytic cells by Listeria monocytogenes. Mol Microbiol 42:955–965

    Article  CAS  PubMed  Google Scholar 

  • Kazazic M, Bertelsen V, Pedersen KW, Vuong TT, Grandal MV, Rodland MS et al (2009) Epsin 1 is involved in recruitment of ubiquitinated EGF receptors into clathrin-coated pits. Traffic 10:235–245

    Article  CAS  PubMed  Google Scholar 

  • Kenny B, DeVinney R, Stein M, Reinscheid DJ, Frey EA, Finlay BB (1997) Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells. Cell 91:511–520

    Article  CAS  PubMed  Google Scholar 

  • Kilsdonk EP, Morel DW, Johnson WJ, Rothblat GH (1995) Inhibition of cellular cholesterol efflux by 25-hydroxycholesterol. J Lipid Res 36:505–516

    CAS  PubMed  Google Scholar 

  • Kirchhausen T, Bonifacino JS, Riezman H (1997) Linking cargo to vesicle formation: receptor tail interactions with coat proteins. Curr Opin Cell Biol 9:488–495

    Article  CAS  PubMed  Google Scholar 

  • Kirkham M, Parton RG (2005) Clathrin-independent endocytosis: new insights into caveolae and non-caveolar lipid raft carriers. Biochim Biophys Acta 1745:273–286

    Article  CAS  PubMed  Google Scholar 

  • Kirkham M, Fujita A, Chadda R, Nixon SJ, Kurzchalia TV, Sharma DK et al (2005) Ultrastructural identification of uncoated caveolin-independent early endocytic vehicles. J Cell Biol 168:465–476

    Article  CAS  PubMed  Google Scholar 

  • Klapisz E, Sorokina I, Lemeer S, Pijnenburg M, Verkleij AJ, van Bergen en Henegouwen PM (2002) A ubiquitin-interacting motif (UIM) is essential for Eps15 and Eps15R ubiquitination. J Biol Chem 277:30746–30753

    Article  CAS  PubMed  Google Scholar 

  • Kuo CC, Chi EY, Grayston JT (1988) Ultrastructural study of entry of Chlamydia strain TWAR into HeLa cells. Infect Immun 56:1668–1672

    CAS  PubMed  Google Scholar 

  • Lafont F, van der Goot FG (2005) Bacterial invasion via lipid rafts. Cell Microbiol 7:613–620

    Article  CAS  PubMed  Google Scholar 

  • Lafont F, Tran Van Nhieu G, Hanada K, Sansonetti P, van der Goot FG (2002) Initial steps of Shigella infection depend on the cholesterol/sphingolipid raft-mediated CD44-IpaB interaction. EMBO J 21:4449–4457

    Article  CAS  PubMed  Google Scholar 

  • Lajoie P, Kojic LD, Nim S, Li L, Dennis JW, Nabi IR (2009) Caveolin-1 regulation of dynamin-dependent, raft-mediated endocytosis of cholera toxin-B sub-unit occurs independently of caveolae. J Cell Mol Med 13:3218–3225

    Article  PubMed  Google Scholar 

  • Laniosz V, Holthusen KA, Meneses PI (2008) Bovine papillomavirus type 1: from clathrin to caveolin. J Virol 82:6288–6298

    Article  CAS  PubMed  Google Scholar 

  • Levy S, Shoham T (2005) Protein-protein interactions in the tetraspanin web. Physiology (Bethesda) 20:218–224

    CAS  Google Scholar 

  • Li S, Galbiati F, Volonte D, Sargiacomo M, Engelman JA, Das K et al (1998) Mutational analysis of caveolin-induced vesicle formation. Expression of caveolin-1 recruits caveolin-2 to caveolae membranes. FEBS Lett 434:127–134

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Kaksonen M, Drubin DG, Oster G (2006) Endocytic vesicle scission by lipid phase boundary forces. Proc Natl Acad Sci U S A 103:10277–10282

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Sun Y, Oster GF, Drubin DG (2010) Mechanochemical crosstalk during endocytic vesicle formation. Curr Opin Cell Biol 22:36–43

    Article  PubMed  CAS  Google Scholar 

  • Macia E, Ehrlich M, Massol R, Boucrot E, Brunner C, Kirchhausen T (2006) Dynasore, a cell-permeable inhibitor of dynamin. Dev Cell 10:839–850

    Article  CAS  PubMed  Google Scholar 

  • Madshus IH, Olsnes S, Sandvig K (1984) Requirements for entry of poliovirus RNA into cells at low pH. EMBO J 3:1945–1950

    CAS  PubMed  Google Scholar 

  • Majeed M, Kihlstrom E (1991) Mobilization of F-actin and clathrin during redistribution of Chlamydia trachomatis to an intracellular site in eucaryotic cells. Infect Immun 59:4465–4472

    CAS  PubMed  Google Scholar 

  • Martinez JJ, Mulvey MA, Schilling JD, Pinkner JS, Hultgren SJ (2000) Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. EMBO J 19:2803–2812

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto T, Miake S, Mitsuyama M, Takeya K, Nomoto K (1982) Enhanced resistance to Listeria monocytogenes due to non-specifically activated macrophages in aged mice. J Clin Lab Immunol 8:51–54

    CAS  PubMed  Google Scholar 

  • Mayor S, Pagano RE (2007) Pathways of clathrin-independent endocytosis. Nat Rev Mol Cell Biol 8:603–612

    Article  CAS  PubMed  Google Scholar 

  • Medigeshi GR, Hirsch AJ, Streblow DN, Nikolich-Zugich J, Nelson JA (2008) West Nile virus entry requires cholesterol-rich membrane microdomains and is independent of alphavbeta3 integrin. J Virol 82:5212–5219

    Article  CAS  PubMed  Google Scholar 

  • Meertens L, Bertaux C, Dragic T (2006) Hepatitis C virus entry requires a critical postinternalization step and delivery to early endosomes via clathrin-coated vesicles. J Virol 80:11571–11578

    Article  CAS  PubMed  Google Scholar 

  • Mercer J, Helenius A (2009) Virus entry by macropinocytosis. Nat Cell Biol 11:510–520

    Article  CAS  PubMed  Google Scholar 

  • Metherall JE, Li H, Waugh K (1996) Role of multidrug resistance P-glycoproteins in cholesterol biosynthesis. J Biol Chem 271:2634–2640

    Article  CAS  PubMed  Google Scholar 

  • Montesano R, Roth J, Robert A, Orci L (1982) Non-coated membrane invaginations are involved in binding and internalization of cholera and tetanus toxins. Nature 296:651–653

    Article  CAS  PubMed  Google Scholar 

  • Moreno-Ruiz E, Galan-Diez M, Zhu W, Fernandez-Ruiz E, d'Enfert C, Filler SG et al (2009) Candida albicans internalization by host cells is mediated by a clathrin-dependent mechanism. Cell Microbiol 11:1179–1189

    Article  CAS  PubMed  Google Scholar 

  • Mousavi SA, Malerod L, Berg T, Kjeken R (2004) Clathrin-dependent endocytosis. Biochem J 377:1–16

    Article  CAS  PubMed  Google Scholar 

  • Mulvey MA, Lopez-Boado YS, Wilson CL, Roth R, Parks WC, Heuser J, Hultgren SJ (1998) Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. Science 282:1494–1497

    Article  CAS  PubMed  Google Scholar 

  • Nichols BJ (2003) GM1-containing lipid rafts are depleted within clathrin-coated pits. Curr Biol 13:686–690

    Article  CAS  PubMed  Google Scholar 

  • Nichols BJ, Lippincott-Schwartz J (2001) Endocytosis without clathrin coats. Trends Cell Biol 11:406–412

    Article  CAS  PubMed  Google Scholar 

  • Nichols BJ, Kenworthy AK, Polishchuk RS, Lodge R, Roberts TH, Hirschberg K et al (2001) Rapid cycling of lipid raft markers between the cell surface and Golgi complex. J Cell Biol 153:529–541

    Article  CAS  PubMed  Google Scholar 

  • Nomura R, Fujimoto T (1999) Tyrosine-phosphorylated caveolin-1: immunolocalization and molecular characterization. Mol Biol Cell 10:975–986

    CAS  PubMed  Google Scholar 

  • Nothwehr SF, Conibear E, Stevens TH (1995) Golgi and vacuolar membrane proteins reach the vacuole in vps1 mutant yeast cells via the plasma membrane. J Cell Biol 129:35–46

    Article  CAS  PubMed  Google Scholar 

  • Oelschlaeger TA, Guerry P, Kopecko DJ (1993) Unusual microtubule-dependent endocytosis mechanisms triggered by Campylobacter jejuni and Citrobacter freundii. Proc Natl Acad Sci U S A 90:6884–6888

    Article  CAS  PubMed  Google Scholar 

  • Oh P, McIntosh DP, Schnitzer JE (1998) 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 141:101–114

    Article  CAS  PubMed  Google Scholar 

  • Oksche A, Boese G, Horstmeyer A, Furkert J, Beyermann M, Bienert M, Rosenthal W (2000) Late endosomal/lysosomal targeting and lack of recycling of the ligand-occupied endothelin B receptor. Mol Pharmacol 57:1104–1113

    CAS  PubMed  Google Scholar 

  • Ono A (2010) Relationships between plasma membrane microdomains and HIV-1 assembly. Biol Cell 102:335–350

    Article  CAS  PubMed  Google Scholar 

  • Orlandi PA, Fishman PH (1998) Filipin-dependent inhibition of cholera toxin: evidence for toxin internalization and activation through caveolae-like domains. J Cell Biol 141:905–915

    Article  CAS  PubMed  Google Scholar 

  • Parolini I, Sargiacomo M, Galbiati F, Rizzo G, Grignani F, Engelman JA et al (1999) Expression of caveolin-1 is required for the transport of caveolin-2 to the plasma membrane. Retention of caveolin-2 at the level of the golgi complex. J Biol Chem 274:25718–25725

    Article  CAS  PubMed  Google Scholar 

  • Parton RG (1994) Ultrastructural localization of gangliosides; GM1 is concentrated in caveolae. J Histochem Cytochem 42:155–166

    CAS  PubMed  Google Scholar 

  • Parton RG, Simons K (2007) The multiple faces of caveolae. Nat Rev Mol Cell Biol 8:185–194

    Article  CAS  PubMed  Google Scholar 

  • Parton RG, Joggerst B, Simons K (1994) Regulated internalization of caveolae. J Cell Biol 127:1199–1215

    Article  CAS  PubMed  Google Scholar 

  • Pelkmans L, Helenius A (2002) Endocytosis via caveolae. Traffic 3:311–320

    Article  CAS  PubMed  Google Scholar 

  • Pietiainen V, Marjomaki V, Upla P, Pelkmans L, Helenius A, Hyypia T (2004) Echovirus 1 endocytosis into caveosomes requires lipid rafts, dynamin II, and signaling events. Mol Biol Cell 15:4911–4925

    Article  PubMed  CAS  Google Scholar 

  • Pucadyil TJ, Schmid SL (2008) Real-time visualization of dynamin-catalyzed membrane fission and vesicle release. Cell 135:1263–1275

    Article  CAS  PubMed  Google Scholar 

  • Pust S, Dyve AB, Torgersen ML, van Deurs B, Sandvig K (2010) Interplay between toxin transport and flotillin localization. PLoS ONE 5:e8844

    Article  PubMed  CAS  Google Scholar 

  • Quirin K, Eschli B, Scheu I, Poort L, Kartenbeck J, Helenius A (2008) Lymphocytic choriomeningitis virus uses a novel endocytic pathway for infectious entry via late endosomes. Virology 378:21–33

    Article  CAS  PubMed  Google Scholar 

  • Razani B, Engelman JA, Wang XB, Schubert W, Zhang XL, Marks CB et al (2001) Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem 276:38121–38138

    Article  CAS  PubMed  Google Scholar 

  • Reig N, van der Goot FG (2006) About lipids and toxins. FEBS Lett 580:5572–5579

    Article  CAS  PubMed  Google Scholar 

  • Rejman J, Oberle V, Zuhorn IS, Hoekstra D (2004) Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem J 377:159–169

    Article  CAS  PubMed  Google Scholar 

  • Robinson MS (1994) The role of clathrin, adaptors and dynamin in endocytosis. Curr Opin Cell Biol 6:538–544

    Article  CAS  PubMed  Google Scholar 

  • Rodal SK, Skretting G, Garred O, Vilhardt F, van Deurs B, Sandvig K (1999) Extraction of cholesterol with methyl-beta-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles. Mol Biol Cell 10:961–974

    CAS  PubMed  Google Scholar 

  • Rodemer C, Haucke V (2008) Clathrin/AP-2-dependent endocytosis: a novel playground for the pharmacological toolbox? Handb Exp Pharmacol 186:105–122

    Article  CAS  PubMed  Google Scholar 

  • Romer W, Pontani LL, Sorre B, Rentero C, Berland L, Chambon V et al (2010) Actin dynamics drive membrane reorganization and scission in clathrin-independent endocytosis. Cell 140:540–553

    Article  CAS  PubMed  Google Scholar 

  • Rosenshine I, Duronio V, Finlay BB (1992) Tyrosine protein kinase inhibitors block invasin-promoted bacterial uptake by epithelial cells. Infect Immun 60:2211–2217

    CAS  PubMed  Google Scholar 

  • Rothberg KG, Heuser JE, Donzell WC, Ying YS, Glenney JR, Anderson RG (1992) Caveolin, a protein component of caveolae membrane coats. Cell 68:673–682

    Article  CAS  PubMed  Google Scholar 

  • Rouquet P, Froment JM, Bermejo M, Kilbourn A, Karesh W, Reed P et al (2005) Wild animal mortality monitoring and human Ebola outbreaks, Gabon and Republic of Congo, 2001-2003. Emerg Infect Dis 11:283–290

    PubMed  Google Scholar 

  • Salcini AE, Chen H, Iannolo G, De Camilli P, Di Fiore PP (1999) Epidermal growth factor pathway substrate 15, Eps15. Int J Biochem Cell Biol 31:805–809

    Article  CAS  PubMed  Google Scholar 

  • Sandvig K (2001) Shiga toxins. Toxicon 39:1629–1635

    Article  CAS  PubMed  Google Scholar 

  • Sandvig K, van Deurs B (1990) Selective modulation of the endocytic uptake of ricin and fluid phase markers without alteration in transferrin endocytosis. J Biol Chem 265:6382–6388

    CAS  PubMed  Google Scholar 

  • Sandvig K, Grimmer S, Lauvrak SU, Torgersen ML, Skretting G, van Deurs B, Iversen TG (2002) Pathways followed by ricin and Shiga toxin into cells. Histochem Cell Biol 117:131–141

    Article  CAS  PubMed  Google Scholar 

  • Sandvig K, Torgersen ML, Raa HA, van Deurs B (2008) Clathrin-independent endocytosis: from nonexisting to an extreme degree of complexity. Histochem Cell Biol 129:267–276

    Article  CAS  PubMed  Google Scholar 

  • Schmid SL (1997) Clathrin-coated vesicle formation and protein sorting: an integrated process. Annu Rev Biochem 66:511–548

    Article  CAS  PubMed  Google Scholar 

  • Schnitzer JE, Oh P, McIntosh DP (1996) Role of GTP hydrolysis in fission of caveolae directly from plasma membranes. Science 274:239–242

    Article  CAS  PubMed  Google Scholar 

  • Scobie HM, Young JA (2005) Interactions between anthrax toxin receptors and protective antigen. Curr Opin Microbiol 8:106–112

    Article  CAS  PubMed  Google Scholar 

  • Shajahan AN, Tiruppathi C, Smrcka AV, Malik AB, Minshall RD (2004) Gbetagamma activation of Src induces caveolae-mediated endocytosis in endothelial cells. J Biol Chem 279:48055–48062

    Article  CAS  PubMed  Google Scholar 

  • Shin JS, Gao Z, Abraham SN (2000) Involvement of cellular caveolae in bacterial entry into mast cells. Science 289:785–788

    Article  CAS  PubMed  Google Scholar 

  • Sigismund S, Woelk T, Puri C, Maspero E, Tacchetti C, Transidico P et al (2005) Clathrin-independent endocytosis of ubiquitinated cargos. Proc Natl Acad Sci U S A 102:2760–2765

    Article  CAS  PubMed  Google Scholar 

  • Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387:569–572

    Article  CAS  PubMed  Google Scholar 

  • Simons K, Toomre D (2000) Lipid rafts and signal transduction. Nat Rev Mol Cell Biol 1:31–39

    Article  CAS  PubMed  Google Scholar 

  • Smart EJ, Estes K, Anderson RG (1995) Inhibitors that block both the internalization of caveolae and the return of plasmalemmal vesicles. Cold Spring Harb Symp Quant Biol 60:243–248

    CAS  PubMed  Google Scholar 

  • Solis GP, Hoegg M, Munderloh C, Schrock Y, Malaga-Trillo E, Rivera-Milla E, Stuermer CA (2007) Reggie/flotillin proteins are organized into stable tetramers in membrane microdomains. Biochem J 403:313–322

    Article  CAS  PubMed  Google Scholar 

  • Sousa S, Cabanes D, Archambaud C, Colland F, Lemichez E, Popoff M et al (2005) ARHGAP10 is necessary for alpha-catenin recruitment at adherens junctions and for Listeria invasion. Nat Cell Biol 7:954–960

    Article  CAS  PubMed  Google Scholar 

  • Spoden G, Freitag K, Husmann M, Boller K, Sapp M, Lambert C, Florin L (2008) Clathrin- and caveolin-independent entry of human papillomavirus type 16—involvement of tetraspanin-enriched microdomains (TEMs). PLoS ONE 3:e3313

    Article  PubMed  CAS  Google Scholar 

  • Stan RV (2002) Structure and function of endothelial caveolae. Microsc Res Tech 57:350–364

    Article  PubMed  Google Scholar 

  • Sullivan RJ, Pantanowitz L, Casper C, Stebbing J, Dezube BJ (2008) HIV/AIDS: epidemiology, pathophysiology, and treatment of Kaposi sarcoma-associated herpesvirus disease: Kaposi sarcoma, primary effusion lymphoma, and multicentric Castleman disease. Clin Infect Dis 47:1209–1215

    Article  PubMed  Google Scholar 

  • Takei K, Yoshida Y, Yamada H (2005) Regulatory mechanisms of dynamin-dependent endocytosis. J Biochem 137:243–247

    Article  CAS  PubMed  Google Scholar 

  • Thali M (2009) The roles of tetraspanins in HIV-1 replication. Curr Top Microbiol Immunol 339:85–102

    Article  CAS  PubMed  Google Scholar 

  • Thomsen P, Roepstorff K, Stahlhut M, van Deurs B (2002) Caveolae are highly immobile plasma membrane microdomains, which are not involved in constitutive endocytic trafficking. Mol Biol Cell 13:238–250

    Article  CAS  PubMed  Google Scholar 

  • Torgersen ML, Skretting G, van Deurs B, Sandvig K (2001) Internalization of cholera toxin by different endocytic mechanisms. J Cell Sci 114:3737–3747

    CAS  PubMed  Google Scholar 

  • Tran D, Carpentier JL, Sawano F, Gorden P, Orci L (1987) Ligands internalized through coated or noncoated invaginations follow a common intracellular pathway. Proc Natl Acad Sci U S A 84:7957–7961

    Article  CAS  PubMed  Google Scholar 

  • Traub LM, Lukacs GL (2007) Decoding ubiquitin sorting signals for clathrin-dependent endocytosis by CLASPs. J Cell Sci 120:543–553

    Article  CAS  PubMed  Google Scholar 

  • Tsuru S, Matsuguchi M, Ohtomo N, Zinnaka Y, Takeya K (1982) Entrance of cholera enterotoxin subunits into cells. J Gen Microbiol 128:497–502

    CAS  PubMed  Google Scholar 

  • Ungewickell EJ, Hinrichsen L (2007) Endocytosis: clathrin-mediated membrane budding. Curr Opin Cell Biol 19:417–425

    Article  CAS  PubMed  Google Scholar 

  • Unsworth KE, Mazurkiewicz P, Senf F, Zettl M, McNiven M, Way M, Holden DW (2007) Dynamin is required for F-actin assembly and pedestal formation by enteropathogenic Escherichia coli (EPEC). Cell Microbiol 9:438–449

    Article  CAS  PubMed  Google Scholar 

  • Utskarpen A, Slagsvold HH, Iversen TG, Walchli S, Sandvig K (2006) Transport of ricin from endosomes to the Golgi apparatus is regulated by Rab6A and Rab6A′. Traffic 7:663–672

    Article  CAS  PubMed  Google Scholar 

  • van Bergen En Henegouwen PM (2009) Eps15: a multifunctional adaptor protein regulating intracellular trafficking. Cell Commun Signal 7:24

    Article  PubMed  CAS  Google Scholar 

  • van der Goot FG, Tran van Nhieu G, Allaoui A, Sansonetti P, Lafont F (2004) Rafts can trigger contact-mediated secretion of bacterial effectors via a lipid-based mechanism. J Biol Chem 279:47792–47798

    Article  PubMed  CAS  Google Scholar 

  • Veiga E, Cossart P (2005) Listeria hijacks the clathrin-dependent endocytic machinery to invade mammalian cells. Nat Cell Biol 7:894–900

    Article  CAS  PubMed  Google Scholar 

  • Veiga E, Guttman JA, Bonazzi M, Boucrot E, Toledo-Arana A, Lin AE et al (2007) Invasive and adherent bacterial pathogens co-Opt host clathrin for infection. Cell Host Microbe 2:340–351

    Article  CAS  PubMed  Google Scholar 

  • Vendeville A, Rayne F, Bonhoure A, Bettache N, Montcourrier P, Beaumelle B (2004) HIV-1 Tat enters T cells using coated pits before translocating from acidified endosomes and eliciting biological responses. Mol Biol Cell 15:2347–2360

    Article  CAS  PubMed  Google Scholar 

  • Watson RO, Galan JE (2008) Campylobacter jejuni survives within epithelial cells by avoiding delivery to lysosomes. PLoS Pathog 4:e14

    Article  PubMed  CAS  Google Scholar 

  • Wolf AA, Fujinaga Y, Lencer WI (2002) Uncoupling of the cholera toxin-G(M1) ganglioside receptor complex from endocytosis, retrograde Golgi trafficking, and downstream signal transduction by depletion of membrane cholesterol. J Biol Chem 277:16249–16256

    Article  CAS  PubMed  Google Scholar 

  • Wooldridge KG, Williams PH, Ketley JM (1996) Host signal transduction and endocytosis of Campylobacter jejuni. Microb Pathog 21:299–305

    Article  CAS  PubMed  Google Scholar 

  • Wyrick PB, Choong J, Davis CH, Knight ST, Royal MO, Maslow AS, Bagnell CR (1989) Entry of genital Chlamydia trachomatis into polarized human epithelial cells. Infect Immun 57:2378–2389

    CAS  PubMed  Google Scholar 

  • Yamamoto N, Yamamoto N, Petroll MW, Cavanagh HD, Jester JV (2005) Internalization of Pseudomonas aeruginosa is mediated by lipid rafts in contact lens-wearing rabbit and cultured human corneal epithelial cells. Invest Ophthalmol Vis Sci 46:1348–1355

    Article  PubMed  Google Scholar 

  • Yanez-Mo M, Barreiro O, Gordon-Alonso M, Sala-Valdes M, Sanchez-Madrid F (2009) Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes. Trends Cell Biol 19:434–446

    Article  CAS  PubMed  Google Scholar 

  • Zaas DW, Duncan MJ, Li G, Wright JR, Abraham SN (2005) Pseudomonas invasion of type I pneumocytes is dependent on the expression and phosphorylation of caveolin-2. J Biol Chem 280:4864–4872

    Article  CAS  PubMed  Google Scholar 

  • Zaas DW, Swan ZD, Brown BJ, Li G, Randell SH, Degan S et al (2009) Counteracting signaling activities in lipid rafts associated with the invasion of lung epithelial cells by Pseudomonas aeruginosa. J Biol Chem 284:9955–9964

    Article  CAS  PubMed  Google Scholar 

  • Zeichhardt H, Otto MJ, McKinlay MA, Willingmann P, Habermehl KO (1987) Inhibition of poliovirus uncoating by disoxaril (WIN 51711). Virology 160:281–285

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Fern Ness for assistance in preparing figures and members of the Guttman Lab for critically reviewing this manuscript. AEL is funded through a Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral Award and the Michael Smith Foundation for Health Research Senior Graduate Studentship. JAG is a CIHR New Investigator. Funding was provided through operating grants from the CIHR and the Natural Sciences and Engineering Research Council of Canada.

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The authors declare that they have no conflicts of interest.

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Lin, A.EJ., Guttman, J.A. Hijacking the endocytic machinery by microbial pathogens. Protoplasma 244, 75–90 (2010). https://doi.org/10.1007/s00709-010-0164-2

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