Recent data have shown that many pathogens are dependent on clathrin and actin for their entry into host cells.
The study of pathogen entry has revealed the flexibility of clathrin to accommodate both large and small cargo.
Different pathogens use different adaptors to fulfil different requirements during the pathogen replication cycle.
It has recently emerged that clathrin functions as a scaffold for actin assembly, in the context of both pathogen infection and cell biology.
The use of endocytic proteins in bacterial infection is conserved, and the proteins used are similar to those used in cell–cell adhesion.
There are several unusual examples of the manipulation of clathrin by pathogens during egress, budding and release.
The role of clathrin in pathogen entry has received much attention and has highlighted the adaptability of clathrin during internalization. Recent studies have now uncovered additional roles for clathrin and have put the spotlight on its role in pathogen spread. Here, we discuss the manipulation of clathrin by pathogens, with specific attention to the processes that occur at the plasma membrane. In the majority of cases, both clathrin and the actin cytoskeleton are hijacked, so we also examine the interplay between these two systems and their role during pathogen internalization, egress and spread.
Subscribe to Journal
Get full journal access for 1 year
only $21.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
McMahon, H. T. & Boucrot, E. Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nature Rev. Mol. Cell Biol. 12, 517–533 (2011).
Traub, L. M. Clathrin couture: fashioning distinctive membrane coats at the cell surface. PLoS Biol. 7, e1000192 (2009).
Brodsky, F. M. Living with clathrin: its role in intracellular membrane traffic. Science 242, 1396–1402 (1988).
Brodsky, F. M., Chen, C. Y., Knuehl, C., Towler, M. C. & Wakeham, D. E. Biological basket weaving: formation and function of clathrin-coated vesicles. Annu. Rev. Cell Dev. Biol. 17, 517–568 (2001).
Owen, D. J., Collins, B. M. & Evans, P. R. Adaptors for clathrin coats: structure and function. Annu. Rev. Cell Dev. Biol. 20, 153–191 (2004).
Robinson, M. S. & Bonifacino, J. S. Adaptor-related proteins. Curr. Opin. Cell Biol. 13, 444–453 (2001).
Dell'Angelica, E. C., Klumperman, J., Stoorvogel, W. & Bonifacino, J. S. Association of the AP-3 adaptor complex with clathrin. Science 280, 431–434 (1998).
Kelly, B. T. & Owen, D. J. Endocytic sorting of transmembrane protein cargo. Curr. Opin. Cell Biol. 23, 404–412 (2011).
Canfield, W. M., Johnson, K. F., Ye, R. D., Gregory, W. & Kornfeld, S. Localization of the signal for rapid internalization of the bovine cation-independent mannose 6-phosphate/insulin-like growth factor-II receptor to amino acids 24–29 of the cytoplasmic tail. J. Biol. Chem. 266, 5682–5688 (1991).
Bresnahan, P. A. et al. A dileucine motif in HIV-1 Nef acts as an internalization signal for CD4 downregulation and binds the AP-1 clathrin adaptor. Curr. Biol. 8, 1235–1238 (1998).
Pond, L. et al. A role for acidic residues in di-leucine motif-based targeting to the endocytic pathway. J. Biol. Chem. 270, 19989–19997 (1995).
Cocucci, E., Aguet, F., Boulant, S. & Kirchhausen, T. The first five seconds in the life of a clathrin-coated pit. Cell 150, 495–507 (2012). Single-molecule live-cell imaging demonstrating that the recruitment of AP2 and clathrin defines the initial steps of endocytosis.
Henne, W. M. et al. FCHo proteins are nucleators of clathrin-mediated endocytosis. Science 328, 1281–1284 (2010). A demonstration of the importance of rim complex proteins in the formation of clathrin-coated vesicles.
McNiven, M. A. & Thompson, H. M. Vesicle formation at the plasma membrane and trans-Golgi network: the same but different. Science 313, 1591–1594 (2006).
Traub, L. M. Common principles in clathrin-mediated sorting at the Golgi and the plasma membrane. Biochim. Biophys. Acta 1744, 415–437 (2005).
Maxfield, F. R. & McGraw, T. E. Endocytic recycling. Nature Rev. Mol. Cell Biol. 5, 121–132 (2004).
Kaksonen, M., Toret, C. P. & Drubin, D. G. Harnessing actin dynamics for clathrin-mediated endocytosis. Nature Rev. Mol. Cell Biol. 7, 404–414 (2006).
Taylor, M. J., Perrais, D. & Merrifield, C. J. A high precision survey of the molecular dynamics of mammalian clathrin-mediated endocytosis. PLoS Biol. 9, e1000604 (2011). Comprehensive live-cell total internal reflection fluorescence (TIRF) imaging analyses of the temporal recruitment of endocytic proteins during vesicle formation.
Collins, A., Warrington, A., Taylor, K. A. & Svitkina, T. Structural organization of the actin cytoskeleton at sites of clathrin-mediated endocytosis. Curr. Biol. 21, 1167–1175 (2011).
Sirotkin, V. Cell biology: actin keeps endocytosis on a short leash. Curr. Biol. 21, R552–R554 (2011).
Boucrot, E., Saffarian, S., Massol, R., Kirchhausen, T. & Ehrlich, M. Role of lipids and actin in the formation of clathrin-coated pits. Exp. Cell Res. 312, 4036–4048 (2006).
Fujimoto, L. M., Roth, R., Heuser, J. E. & Schmid, S. L. Actin assembly plays a variable, but not obligatory role in receptor-mediated endocytosis in mammalian cells. Traffic 1, 161–171 (2000).
Yarar, D., Waterman-Storer, C. M. & Schmid, S. L. A dynamic actin cytoskeleton functions at multiple stages of clathrin-mediated endocytosis. Mol. Biol. Cell 16, 964–975 (2005).
Batchelder, E. M. & Yarar, D. Differential requirements for clathrin-dependent endocytosis at sites of cell-substrate adhesion. Mol. Biol. Cell 21, 3070–3079 (2010).
Boulant, S., Kural, C., Zeeh, J. C., Ubelmann, F. & Kirchhausen, T. Actin dynamics counteract membrane tension during clathrin-mediated endocytosis. Nature Cell Biol. 13, 1124–1131 (2011). A study that resolves the controversy of the role of actin during mammalian endocytosis.
Liu, A. P., Loerke, D., Schmid, S. L. & Danuser, G. Global and local regulation of clathrin-coated pit dynamics detected on patterned substrates. Biophys. J. 97, 1038–1047 (2009).
Saffarian, S., Cocucci, E. & Kirchhausen, T. Distinct dynamics of endocytic clathrin-coated pits and coated plaques. PLoS Biol. 7, e1000191 (2009). The first detailed analysis of the dynamics and behaviour of clathrin plaques.
Gauthier, N. C., Masters, T. A. & Sheetz, M. P. Mechanical feedback between membrane tension and dynamics. Trends Cell Biol. 22, 527–535 (2012).
Aghamohammadzadeh, S. & Ayscough, K. R. Differential requirements for actin during yeast and mammalian endocytosis. Nature Cell Biol. 11, 1039–1042 (2009).
Campellone, K. G. & Welch, M. D. A nucleator arms race: cellular control of actin assembly. Nature Rev. Mol. Cell Biol. 11, 237–251 (2010).
Benesch, S. et al. N-WASP deficiency impairs EGF internalization and actin assembly at clathrin-coated pits. J. Cell Sci. 118, 3103–3115 (2005).
Innocenti, M. et al. Abi1 regulates the activity of N-WASP and WAVE in distinct actin-based processes. Nature Cell Biol. 7, 969–976 (2005).
Merrifield, C. J. Seeing is believing: imaging actin dynamics at single sites of endocytosis. Trends Cell Biol. 14, 352–358 (2004).
Ferguson, S. M. & De Camilli, P. Dynamin, a membrane-remodelling GTPase. Nature Rev. Mol. Cell Biol. 13, 75–88 (2012).
Faelber, K. et al. Crystal structure of nucleotide-free dynamin. Nature 477, 556–560 (2011).
Weaver, A. M. et al. Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation. Curr. Biol. 11, 370–374 (2001).
Higgs, H. Branching out: cortactin stabilizes actin networks generated by the Arp2/3 complex. Trends Biochem. Sci. 26, 219 (2001).
Uruno, T. et al. Activation of Arp2/3 complex-mediated actin polymerization by cortactin. Nature Cell Biol. 3, 259–266 (2001).
McNiven, M. A. et al. Regulated interactions between dynamin and the actin-binding protein cortactin modulate cell shape. J. Cell Biol. 151, 187–198 (2000).
Engqvist-Goldstein, A. E., Kessels, M. M., Chopra, V. S., Hayden, M. R. & Drubin, D. G. An actin-binding protein of the Sla2/Huntingtin interacting protein 1 family is a novel component of clathrin-coated pits and vesicles. J. Cell Biol. 147, 1503–1518 (1999).
Engqvist-Goldstein, A. E. et al. The actin-binding protein Hip1R associates with clathrin during early stages of endocytosis and promotes clathrin assembly in vitro. J. Cell Biol. 154, 1209–1223 (2001).
Wilbur, J. D. et al. Actin binding by Hip1 (huntingtin-interacting protein 1) and Hip1R (Hip1-related protein) is regulated by clathrin light chain. J. Biol. Chem. 283, 32870–32879 (2008).
Le Clainche, C. et al. A Hip1R-cortactin complex negatively regulates actin assembly associated with endocytosis. EMBO J. 26, 1199–1210 (2007).
Lai, F. P. et al. Cortactin promotes migration and platelet-derived growth factor-induced actin reorganization by signaling to Rho-GTPases. Mol. Biol. Cell 20, 3209–3223 (2009).
Chetrit, D., Ziv, N. & Ehrlich, M. Dab2 regulates clathrin assembly and cell spreading. Biochem. J. 418, 701–715 (2009).
Johannes, L. & Popoff, V. Tracing the retrograde route in protein trafficking. Cell 135, 1175–1187 (2008).
Raiborg, C. et al. Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes. Nature Cell Biol. 4, 394–398 (2002).
Futter, C. E. et al. In polarized MDCK cells basolateral vesicles arise from clathrin-γ-adaptin-coated domains on endosomal tubules. J. Cell Biol. 141, 611–623 (1998).
Sachse, M., Urbe, S., Oorschot, V., Strous, G. J. & Klumperman, J. Bilayered clathrin coats on endosomal vacuoles are involved in protein sorting toward lysosomes. Mol. Biol. Cell 13, 1313–1328 (2002).
Raiborg, C., Wesche, J., Malerod, L. & Stenmark, H. Flat clathrin coats on endosomes mediate degradative protein sorting by scaffolding Hrs in dynamic microdomains. J. Cell Sci. 119, 2414–2424 (2006).
Itoh, T. et al. Role of the ENTH domain in phosphatidylinositol-4,5-bisphosphate binding and endocytosis. Science 291, 1047–1051 (2001).
Ford, M. G. et al. Curvature of clathrin-coated pits driven by epsin. Nature 419, 361–366 (2002).
Repass, S. L., Brady, R. J. & O'Halloran, T. J. Dictyostelium Hip1r contributes to spore shape and requires epsin for phosphorylation and localization. J. Cell Sci. 120, 3977–3988 (2007).
Brady, R. J., Damer, C. K., Heuser, J. E. & O'Halloran, T. J. Regulation of Hip1r by epsin controls the temporal and spatial coupling of actin filaments to clathrin-coated pits. J. Cell Sci. 123, 3652–3661 (2010).
Davey, N. E., Trave, G. & Gibson, T. J. How viruses hijack cell regulation. Trends Biochem. Sci. 36, 159–169 (2011).
Dodding, M. P. & Way, M. Coupling viruses to dynein and kinesin-1. EMBO J. 30, 3527–3539 (2011).
Rahman, M. M. & McFadden, G. Modulation of NF-κB signalling by microbial pathogens. Nature Rev. Microbiol. 9, 291–306 (2011).
Taylor, M. P., Koyuncu, O. O. & Enquist, L. W. Subversion of the actin cytoskeleton during viral infection. Nature Rev. Microbiol. 9, 427–439 (2011).
Cossart, P. & Veiga, E. Non-classical use of clathrin during bacterial infections. J. Microsc. 231, 524–528 (2008).
Gruenberg, J. Viruses and endosome membrane dynamics. Curr. Opin. Cell Biol. 21, 582–588 (2009).
Marsh, M. & Helenius, A. Virus entry: open sesame. Cell 124, 729–740 (2006).
Mercer, J., Schelhaas, M. & Helenius, A. Virus entry by endocytosis. Annu. Rev. Biochem. 79, 803–833 (2010).
Schelhaas, M. Come in and take your coat off – how host cells provide endocytosis for virus entry. Cell. Microbiol. 12, 1378–1388 (2010).
Swanson, J. A. Shaping cups into phagosomes and macropinosomes. Nature Rev. Mol. Cell Biol. 9, 639–649 (2008).
Swanson, J. A. & Watts, C. Macropinocytosis. Trends Cell Biol. 5, 424–428 (1995).
Cheng, Y., Boll, W., Kirchhausen, T., Harrison, S. C. & Walz, T. Cryo-electron tomography of clathrin-coated vesicles: structural implications for coat assembly. J. Mol. Biol. 365, 892–899 (2007).
Ehrlich, M. et al. Endocytosis by random initiation and stabilization of clathrin-coated pits. Cell 118, 591–605 (2004).
McMahon, H. T. Endocytosis: an assembly protein for clathrin cages. Curr. Biol. 9, R332–R335 (1999).
Fotin, A. et al. Molecular model for a complete clathrin lattice from electron cryomicroscopy. Nature 432, 573–579 (2004).
Cureton, D. K., Massol, R. H., Saffarian, S., Kirchhausen, T. L. & Whelan, S. P. Vesicular stomatitis virus enters cells through vesicles incompletely coated with clathrin that depend upon actin for internalization. PLoS Pathog. 5, e1000394 (2009).
Cureton, D. K., Massol, R. H., Whelan, S. P. & Kirchhausen, T. The length of vesicular stomatitis virus particles dictates a need for actin assembly during clathrin-dependent endocytosis. PLoS Pathog. 6, e1001127 (2010). A seminal study showing the role of actin and the flexibility of clathrin during pathogen internalization.
Johannsdottir, H. K., Mancini, R., Kartenbeck, J., Amato, L. & Helenius, A. Host cell factors and functions involved in vesicular stomatitis virus entry. J. Virol. 83, 440–453 (2009).
Bonazzi, M., Veiga, E., Pizarro-Cerda, J. & Cossart, P. Successive post-translational modifications of E-cadherin are required for InlA-mediated internalization of Listeria monocytogenes. Cell. Microbiol. 10, 2208–2222 (2008).
Moreno-Ruiz, E. et al. Candida albicans internalization by host cells is mediated by a clathrin-dependent mechanism. Cell. Microbiol. 11, 1179–1189 (2009).
Veiga, E. et al. Invasive and adherent bacterial pathogens co-opt host clathrin for infection. Cell Host Microbe 2, 340–351 (2007). A comprehensive investigation of the recruitment and role of clathrin during bacterial internalization.
Pizarro-Cerda, J., Bonazzi, M. & Cossart, P. Clathrin-mediated endocytosis: what works for small, also works for big. Bioessays 32, 496–504 (2010).
Brodsky, F. M. Diversity of clathrin function: new tricks for an old protein. Annu. Rev. Cell Dev. Biol. 28, 309–336 (2012).
Campellone, K. G. Cytoskeleton-modulating effectors of enteropathogenic and enterohaemorrhagic Escherichia coli: Tir, EspFU and actin pedestal assembly. FEBS J. 277, 2390–2402 (2010).
Kenny, B. et al. Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells. Cell 91, 511–520 (1997).
Phillips, N., Hayward, R. D. & Koronakis, V. Phosphorylation of the enteropathogenic E. coli receptor by the Src-family kinase c-Fyn triggers actin pedestal formation. Nature Cell Biol. 6, 618–625 (2004).
Swimm, A., Bommarius, B., Reeves, P., Sherman, M. & Kalman, D. Complex kinase requirements for EPEC pedestal formation. Nature Cell Biol 6, 795; author reply 795–796 (2004).
Campellone, K. G. & Leong, J. M. Nck-independent actin assembly is mediated by two phosphorylated tyrosines within enteropathogenic Escherichia coli Tir. Mol. Microbiol. 56, 416–432 (2005).
Gruenheid, S. et al. Enteropathogenic E. coli Tir binds Nck to initiate actin pedestal formation in host cells. Nature Cell Biol. 3, 856–859 (2001).
Kenny, B. Phosphorylation of tyrosine 474 of the enteropathogenic Escherichia coli (EPEC) Tir receptor molecule is essential for actin nucleating activity and is preceded by additional host modifications. Mol. Microbiol. 31, 1229–1241 (1999).
Rosenshine, I. et al. A pathogenic bacterium triggers epithelial signals to form a functional bacterial receptor that mediates actin pseudopod formation. EMBO J. 15, 2613–2624 (1996).
Kalman, D. et al. Enteropathogenic E. coli acts through WASP and Arp2/3 complex to form actin pedestals. Nature Cell Biol. 1, 389–391 (1999).
Lommel, S. et al. Actin pedestal formation by enteropathogenic Escherichia coli and intracellular motility of Shigella flexneri are abolished in N-WASP-defective cells. EMBO Rep. 2, 850–857 (2001).
Unsworth, K. E. et al. Dynamin is required for F-actin assembly and pedestal formation by enteropathogenic Escherichia coli (EPEC). Cell. Microbiol. 9, 438–449 (2007).
Lin, A. E., Benmerah, A. & Guttman, J. A. Eps15 and epsin1 are crucial for enteropathogenic Escherichia coli pedestal formation despite the absence of adaptor protein 2. J. Infect. Dis. 204, 695–703 (2011).
Cossart, P. & Sansonetti, P. J. Bacterial invasion: the paradigms of enteroinvasive pathogens. Science 304, 242–248 (2004).
Veiga, E. & Cossart, P. Listeria hijacks the clathrin-dependent endocytic machinery to invade mammalian cells. Nature Cell Biol. 7, 894–900 (2005). The first study to demonstrate that the endocytic machinery is key to bacterial internalization.
Guttman, J. A., Lin, A. E., Veiga, E., Cossart, P. & Finlay, B. B. Role for CD2AP and other endocytosis-associated proteins in enteropathogenic Escherichia coli pedestal formation. Infect. Immun. 78, 3316–3322 (2010).
Lee, E. & De Camilli, P. Dynamin at actin tails. Proc. Natl Acad. Sci. USA 99, 161–166 (2002).
Bonazzi, M. et al. A common clathrin-mediated machinery co-ordinates cell-cell adhesion and bacterial internalization. Traffic 13, 1653–1666 (2012).
Bonazzi, M. et al. Clathrin phosphorylation is required for actin recruitment at sites of bacterial adhesion and internalization. J. Cell Biol. 195, 525–536 (2011). Work highlighting the importance of clathrin heavy chain phosphorylation in stabilizing the clathrin coat and creating a platform for actin assembly.
Beattie, E. C., Howe, C. L., Wilde, A., Brodsky, F. M. & Mobley, W. C. NGF signals through TrkA to increase clathrin at the plasma membrane and enhance clathrin-mediated membrane trafficking. J. Neurosci. 20, 7325–7333 (2000).
Wilde, A. et al. EGF receptor signaling stimulates SRC kinase phosphorylation of clathrin, influencing clathrin redistribution and EGF uptake. Cell 96, 677–687 (1999).
Yonemura, S. Cadherin-actin interactions at adherens junctions. Curr. Opin. Cell Biol. 23, 515–522 (2011).
Brasch, J., Harrison, O. J., Honig, B. & Shapiro, L. Thinking outside the cell: how cadherins drive adhesion. Trends Cell Biol. 22, 299–310 (2012).
Lecuit, M. et al. A single amino acid in E-cadherin responsible for host specificity towards the human pathogen Listeria monocytogenes. EMBO J. 18, 3956–3963 (1999).
Bonazzi, M. & Cossart, P. Impenetrable barriers or entry portals? The role of cell–cell adhesion during infection. J. Cell Biol. 195, 349–358 (2011).
Keyel, P. A. et al. A single common portal for clathrin-mediated endocytosis of distinct cargo governed by cargo-selective adaptors. Mol. Biol. Cell 17, 4300–4317 (2006).
Maurer, M. E. & Cooper, J. A. The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH. J. Cell Sci. 119, 4235–4246 (2006).
Mishra, S. K. et al. Disabled-2 exhibits the properties of a cargo-selective endocytic clathrin adaptor. EMBO J. 21, 4915–4926 (2002).
Motley, A., Bright, N. A., Seaman, M. N. & Robinson, M. S. Clathrin-mediated endocytosis in AP-2-depleted cells. J. Cell Biol. 162, 909–918 (2003).
Traub, L. M. Sorting it out: AP-2 and alternate clathrin adaptors in endocytic cargo selection. J. Cell Biol. 163, 203–208 (2003).
Teckchandani, A., Mulkearns, E. E., Randolph, T. W., Toida, N. & Cooper, J. A. The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin β1 endocytosis. Mol. Biol. Cell 23, 2905–2916 (2012).
Mulkearns, E. E. & Cooper, J. A. FCH domain only-2 organizes clathrin-coated structures and interacts with Disabled-2 for low-density lipoprotein receptor endocytosis. Mol. Biol. Cell 23, 1330–1342 (2012).
Chen, H. et al. Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis. Nature 394, 793–797 (1998).
Shih, S. C. et al. Epsins and Vps27p/Hrs contain ubiquitin-binding domains that function in receptor endocytosis. Nature Cell Biol. 4, 389–393 (2002).
Yamabhai, M. et al. Intersectin, a novel adaptor protein with two Eps15 homology and five Src homology 3 domains. J. Biol. Chem. 273, 31401–31407 (1998).
Wendland, B. Epsins: adaptors in endocytosis? Nature Rev. Mol. Cell Biol. 3, 971–977 (2002).
Haglund, C. M. & Welch, M. D. Pathogens and polymers: microbe–host interactions illuminate the cytoskeleton. J. Cell Biol. 195, 7–17 (2011).
Zhang, F., Zang, T., Wilson, S. J., Johnson, M. C. & Bieniasz, P. D. Clathrin facilitates the morphogenesis of retrovirus particles. PLoS Pathog. 7, e1002119 (2011). An analysis of the role of clathrin during retroviral assembly and budding.
Huang, C., Chang, S. C., Yang, H. C., Chien, C. L. & Chang, M. F. Clathrin-mediated post-Golgi membrane trafficking in the morphogenesis of hepatitis delta virus. J. Virol. 83, 12314–12324 (2009).
Huang, C., Chang, S. C., Yu, I. C., Tsay, Y. G. & Chang, M. F. Large hepatitis delta antigen is a novel clathrin adaptor-like protein. J. Virol. 81, 5985–5994 (2007).
Wang, Y. C., Huang, C. R., Chao, M. & Lo, S. J. The C-terminal sequence of the large hepatitis delta antigen is variable but retains the ability to bind clathrin. Virol. J. 6, 31 (2009).
Fukumatsu, M. et al. Shigella targets epithelial tricellular junctions and uses a noncanonical clathrin-dependent endocytic pathway to spread between cells. Cell Host Microbe 11, 325–336 (2012).
Humphries, A. C. et al. Clathrin potentiates vaccinia-induced actin polymerization to facilitate viral spread. Cell Host Microbe 12, 346–359 (2012). An unexpected role for clathrin-mediated promotion of actin assembly during vaccinia virus egress.
May, R. C. & Machesky, L. M. Plagiarism and pathogenesis: common themes in actin remodeling. Dev. Cell 1, 317–318 (2001).
Frischknecht, F. & Way, M. Surfing pathogens and the lessons learned for actin polymerization. Trends Cell Biol. 11, 30–38 (2001).
Schmelz, M. et al. Assembly of vaccinia virus: the second wrapping cisterna is derived from the trans Golgi network. J. Virol. 68, 130–147 (1994).
Tooze, J., Hollinshead, M., Reis, B., Radsak, K. & Kern, H. Progeny vaccinia and human cytomegalovirus particles utilize early endosomal cisternae for their envelopes. Eur. J. Cell Biol. 60, 163–178 (1993).
Roberts, K. L. & Smith, G. L. Vaccinia virus morphogenesis and dissemination. Trends Microbiol. 16, 472–479 (2008).
Dodding, M. P., Mitter, R., Humphries, A. C. & Way, M. A kinesin-1 binding motif in vaccinia virus that is widespread throughout the human genome. EMBO J. 30, 4523–4538 (2011).
Newsome, T. P., Scaplehorn, N. & Way, M. SRC mediates a switch from microtubule- to actin-based motility of vaccinia virus. Science 306, 124–129 (2004).
Rietdorf, J. et al. Kinesin-dependent movement on microtubules precedes actin-based motility of vaccinia virus. Nature Cell Biol. 3, 992–1000 (2001).
Hollinshead, M. et al. Vaccinia virus utilizes microtubules for movement to the cell surface. J. Cell Biol. 154, 389–402 (2001).
Geada, M. M., Galindo, I., Lorenzo, M. M., Perdiguero, B. & Blasco, R. Movements of vaccinia virus intracellular enveloped virions with GFP tagged to the F13L envelope protein. J. Gen. Virol. 82, 2747–2760 (2001).
Ward, B. M. & Moss, B. Vaccinia virus A36R membrane protein provides a direct link between intracellular enveloped virions and the microtubule motor kinesin. J. Virol. 78, 2486–2493 (2004).
Frischknecht, F. et al. Actin-based motility of vaccinia virus mimics receptor tyrosine kinase signalling. Nature 401, 926–929 (1999).
Scaplehorn, N. et al. Grb2 and Nck act cooperatively to promote actin-based motility of vaccinia virus. Curr. Biol. 12, 740–745 (2002).
Reeves, P. M. et al. Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases. Nature Med. 11, 731–739 (2005).
Newsome, T. P., Weisswange, I., Frischknecht, F. & Way, M. Abl collaborates with Src family kinases to stimulate actin-based motility of vaccinia virus. Cell. Microbiol. 8, 233–241 (2006).
Moreau, V. et al. A complex of N-WASP and WIP integrates signalling cascades that lead to actin polymerization. Nature Cell Biol. 2, 441–448 (2000).
Weisswange, I., Newsome, T. P., Schleich, S. & Way, M. The rate of N-WASP exchange limits the extent of ARP2/3-complex-dependent actin-based motility. Nature 458, 87–91 (2009).
Doceul, V., Hollinshead, M., van der Linden, L. & Smith, G. L. Repulsion of superinfecting virions: a mechanism for rapid virus spread. Science 327, 873–876 (2010).
Cudmore, S., Cossart, P., Griffiths, G. & Way, M. Actin-based motility of vaccinia virus. Nature 378, 636–638 (1995).
Donnelly, S. K., Weisswange, I., Zettl, M. & Way, M. WIP provides an essential link between Nck and N-WASP during Arp2/3-dependent actin polymerization. Curr. Biol. 23, 999–1006 (2013).
Serio, A. W., Jeng, R. L., Haglund, C. M., Reed, S. C. & Welch, M. D. Defining a core set of actin cytoskeletal proteins critical for actin-based motility of Rickettsia. Cell Host Microbe 7, 388–398 (2010).
Horsington, J. et al. A36-dependent actin filament nucleation promotes release of vaccinia virus. PLoS Pathog. 9, e1003239 (2013).
Husain, M. & Moss, B. Intracellular trafficking of a palmitoylated membrane-associated protein component of enveloped vaccinia virus. J. Virol. 77, 9008–9019 (2003).
Husain, M. & Moss, B. Role of receptor-mediated endocytosis in the formation of vaccinia virus extracellular enveloped particles. J. Virol. 79, 4080–4089 (2005).
Van Vliet, K. et al. Poxvirus proteomics and virus-host protein interactions. Microbiol. Mol. Biol. Rev. 73, 730–749 (2009).
Blasco, R., Sisler, J. R. & Moss, B. Dissociation of progeny vaccinia virus from the cell membrane is regulated by a viral envelope glycoprotein: effect of a point mutation in the lectin homology domain of the A34R gene. J. Virol. 67, 3319–3325 (1993).
Katz, E., Ward, B. M., Weisberg, A. S. & Moss, B. Mutations in the vaccinia virus A33R and B5R envelope proteins that enhance release of extracellular virions and eliminate formation of actin-containing microvilli without preventing tyrosine phosphorylation of the A36R protein. J. Virol. 77, 12266–12275 (2003).
Katz, E., Wolffe, E. & Moss, B. Identification of second-site mutations that enhance release and spread of vaccinia virus. J. Virol. 76, 11637–11644 (2002).
Payne, L. G. Significance of extracellular enveloped virus in the in vitro and in vivo dissemination of vaccinia. J. Gen. Virol. 50, 89–100 (1980).
Blasco, R. & Moss, B. Role of cell-associated enveloped vaccinia virus in cell-to-cell spread. J. Virol. 66, 4170–4179 (1992).
Smith, G. L. & Law, M. The exit of vaccinia virus from infected cells. Virus Res. 106, 189–197 (2004).
Delchambre, M. et al. The GAG precursor of simian immunodeficiency virus assembles into virus-like particles. EMBO J. 8, 2653–2660 (1989).
Gheysen, D. et al. Assembly and release of HIV-1 precursor Pr55gag virus-like particles from recombinant baculovirus-infected insect cells. Cell 59, 103–112 (1989).
Morita, E. & Sundquist, W. I. Retrovirus budding. Annu. Rev. Cell Dev. Biol. 20, 395–425 (2004).
Henne, W. M., Buchkovich, N. J. & Emr, S. D. The ESCRT pathway. Dev. Cell 21, 77–91 (2011).
Puffer, B. A., Watkins, S. C. & Montelaro, R. C. Equine infectious anemia virus Gag polyprotein late domain specifically recruits cellular AP-2 adapter protein complexes during virion assembly. J. Virol. 72, 10218–10221 (1998).
Batonick, M. et al. Interaction of HIV-1 Gag with the clathrin-associated adaptor AP-2. Virology 342, 190–200 (2005).
Camus, G. et al. The clathrin adaptor complex AP-1 binds HIV-1 and MLV Gag and facilitates their budding. Mol. Biol. Cell 18, 3193–3203 (2007).
Chen, C., Weisz, O. A., Stolz, D. B., Watkins, S. C. & Montelaro, R. C. Differential effects of actin cytoskeleton dynamics on equine infectious anemia virus particle production. J. Virol. 78, 882–891 (2004).
Gladnikoff, M., Shimoni, E., Gov, N. S. & Rousso, I. Retroviral assembly and budding occur through an actin-driven mechanism. Biophys. J. 97, 2419–2428 (2009).
Jolly, C., Mitar, I. & Sattentau, Q. J. Requirement for an intact T-cell actin and tubulin cytoskeleton for efficient assembly and spread of human immunodeficiency virus type 1. J. Virol. 81, 5547–5560 (2007).
Sasaki, H. et al. Myosin–actin interaction plays an important role in human immunodeficiency virus type 1 release from host cells. Proc. Natl Acad. Sci. USA 92, 2026–2030 (1995).
Dube, M. et al. Antagonism of tetherin restriction of HIV-1 release by Vpu involves binding and sequestration of the restriction factor in a perinuclear compartment. PLoS Pathog. 6, e1000856 (2010).
Kueck, T. & Neil, S. J. A cytoplasmic tail determinant in HIV-1 Vpu mediates targeting of tetherin for endosomal degradation and counteracts interferon-induced restriction. PLoS Pathog. 8, e1002609 (2012).
Zhang, F. et al. SIV Nef proteins recruit the AP-2 complex to antagonize Tetherin and facilitate virion release. PLoS Pathog. 7, e1002039 (2011).
Martin-Serrano, J. & Neil, S. J. Host factors involved in retroviral budding and release. Nature Rev. Microbiol. 9, 519–531 (2011).
The authors thank members of the Way laboratory for comments on the text.
The authors declare no competing financial interests.
About this article
Cite this article
Humphries, A., Way, M. The non-canonical roles of clathrin and actin in pathogen internalization, egress and spread. Nat Rev Microbiol 11, 551–560 (2013). https://doi.org/10.1038/nrmicro3072
Proteins involved in actin filament organization are key host factors for Japanese encephalitis virus life-cycle in human neuronal cells
Microbial Pathogenesis (2020)
Frontiers in Cellular and Infection Microbiology (2020)
Microbiology and Molecular Biology Reviews (2019)
Journal of Cell Science (2019)