Skip to main content
SpringerLink
Log in

The Role of MACPF Proteins in the Biology of Malaria and Other Apicomplexan Parasites

  • Chapter
  • First Online:
MACPF/CDC Proteins - Agents of Defence, Attack and Invasion

Part of the book series: Subcellular Biochemistry ((SCBI,volume 80))

Abstract

Apicomplexans are eukaryotic parasites of major medical and veterinary importance. They have complex life cycles through frequently more than one host, interact with many cell types in their hosts, and can breach host cell membranes during parasite traversal of, or egress from, host cells. Some of these parasites make a strikingly heavy use of the pore-forming MACPF domain, and encode up to 10 different MACPF domain-containing proteins. In this chapter, we focus on the two most studied and medically important apicomplexans, Plasmodium and Toxoplasma, and describe the known functions of their MACPF polypeptide arsenal. Apicomplexan MACPF proteins appear to be involved in a variety of membrane-damaging events, making them an attractive model to dissect the structure-function relationships of the MACPF domain.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

APC-β:

Apicomplexan perforin-like protein C-terminal β-sheet

CAD1:

Constitutively activated cell death 1

CCP:

Complement control protein

CDCs:

Cholesterol-dependent cytolysins

EPM:

Erythrocyte plasma membrane

FIMAC :

Factor I membrane attack complex

HPM:

Hepatocyte plasma membrane

LDL-A:

Low density lipoprotein receptor domain A

MACPF:

Membrane-attack complex/perforin

MACPFapi :

MACPF domains of apicomplexans

MAOP:

Membrane-attack ookinete protein

PLP:

Perforin-like protein

PPLP:

Plasmodium perforin-like protein

PV:

Parasitophorous vacuole

PVM:

Parasitophorous vacuole membrane

RBC:

Red blood cell

SCR:

Short consensus repeats

SPECT:

Sporozoite microneme protein essential for cell traversal

TSR:

Thrombospondin type I repat

WT:

Wild type

References

  1. Amino R, Giovannini D, Thiberge S, Gueirard P, Boisson B, Dubremetz JF, Prévost MC, Ishino T, Yuda M, Ménard R (2008) Host cell traversal is important for progression of the malaria parasite through the dermis to the liver. Cell Host Microbe 3:88–96

    Article  CAS  PubMed  Google Scholar 

  2. Arastu-Kapur S, Ponder EL, Fonović UP, Yeoh S, Yuan F, Fonović M, Grainger M, Phillips CI, Powers JC, Bogyo M (2008) Identification of proteases that regulate erythrocyte rupture by the malaria parasite Plasmodium falciparum. Nat Chem Biol 4:203–213

    Article  CAS  PubMed  Google Scholar 

  3. Baer K, Klotz C, Kappe SH, Schnieder T, Frevert U (2007) Release of hepatic Plasmodium yoelii merozoites into the pulmonary microvasculature. PLoS Pathog 3:e171

    Article  PubMed Central  PubMed  Google Scholar 

  4. Bargieri D, Lagal V, Tardieux I, Ménard R (2012) Host cell invasion by apicomplexans: what do we know? Trends Parasitol 28:131–135

    Article  CAS  PubMed  Google Scholar 

  5. Blackman MJ (2008) Malarial proteases and host cell egress: an ‘emerging’ cascade. Cell Microbiol 10:1925–1934

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Chalmers RM, Giles M (2010) Zoonotic cryptosporidiosis in the UK—challenges for control. J Appl Microbiol 109:1487–1497

    Article  CAS  PubMed  Google Scholar 

  7. Chandramohanadas R, Davis PH, Beiting DP, Harbut MB, Darling C, Velmourougane G, Lee MY, Greer PA, Roos DS, Greenbaum DC (2009) Apicomplexan parasites co-opt host calpains to facilitate their escape from infected cells. Science 324:794–797

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Cowman AF, Berry D, Baum J (2012) The cellular and molecular basis for malaria parasite invasion of the human red blood cell. J Cell Biol 198:961–971

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Deligianni E, Morgan RN, Bertuccini L, Wirth CC, Silmon de Monerri NC, Spanos L, Blackman MJ, Louis C, Pradel G, Siden-Kiamos I (2013) A perforin-like protein mediates disruption of the erythrocyte membrane during egress of Plasmodium berghei male gametocytes. Cell Microbiol 15:1438–1455

    Google Scholar 

  10. Ecker A, Pinto SB, Baker KW, Kafatos FC, Sinden RE (2007) Plasmodium berghei: Plasmodium perforin-like protein 5 is required for mosquito midgut invasion in Anopheles stephensi. Exp Parasitol 116:504–508

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Ecker A, Bushell ES, Tewari R, Sinden RE (2008) Reverse genetics screen identifies six proteins important for malaria development in the mosquito. Mol Microbiol 70:209–220

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Graewe S, Rankin KE, Lehmann C, Deschermeier C, Hecht L, Froehlke U, Stanway RR, Heussler V (2011) Hostile takeover by Plasmodium: reorganization of parasite and host cell membranes during liver stage egress. PLoS Pathog 7:e1002224

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Hadders MA, Beringer DX, Gros P (2007) Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense. Science 317:1552–1554

    Article  CAS  PubMed  Google Scholar 

  14. Hall N, Karras M, Raine JD, Carlton JM, Kooij TW, Berriman M, Florens L, Janssen CS, Pain A, Christophides GK, James K, Rutherford K, Harris B, Harris D, Churcher C, Quail MA, Ormond D, Doggett J, Trueman HE, Mendoza J, Bidwell SL, Rajandream MA, Carucci DJ, Yates JR 3rd, Kafatos FC, Janse CJ, Barrell B, Turner CM, Waters AP, Sinden RE (2005) A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses. Science 307:82–86

    Article  CAS  PubMed  Google Scholar 

  15. Innes EA (2010) A brief history and overview of Toxoplasma gondii. Zoonoses Public Health 57:1–7

    Article  CAS  PubMed  Google Scholar 

  16. Ishino T, Yano K, Chinzei Y, Yuda M (2004) Cell-passage activity is required for the malarial parasite to cross the liver sinusoidal cell layer. PLoS Biol 2:E4

    Article  PubMed Central  PubMed  Google Scholar 

  17. Ishino T, Chinzei Y, Yuda M (2005) A Plasmodium sporozoite protein with a membrane attack complex domain is required for breaching the liver sinusoidal cell layer prior to hepatocyte infection. Cell Microbiol 7:199–208

    Article  CAS  PubMed  Google Scholar 

  18. Kadota K, Ishino T, Matsuyama T, Chinzei Y, Yuda M (2004) Essential role of membrane-attack protein in malarial transmission to mosquito host. Proc Natl Acad Sci USA 101:16310–16315

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Kafsack BF, Pena JD, Coppens I, Ravindran S, Boothroyd JC, Carruthers VB (2009) Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells. Science 323:530–533

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Kafsack BF, Carruthers VB (2010) Apicomplexan perforin-like proteins. Commun Integr Biol 3:18–23

    Article  PubMed Central  PubMed  Google Scholar 

  21. Kaiser K, Camargo N, Coppens I, Morrisey JM, Vaidya AB, Kappe SH (2004) A member of a conserved Plasmodium protein family with membrane-attack complex/perforin (MACPF)-like domains localizes to the micronemes of sporozoites. Mol Biochem Parasitol 133:15–26

    Article  CAS  PubMed  Google Scholar 

  22. Mota MM, Pradel G, Vanderberg JP, Hafalla JC, Frevert U, Nussenzweig RS, Nussenzweig V, Rodríguez A (2001) Migration of Plasmodium sporozoites through cells before infection. Science 291:141–144

    Article  CAS  PubMed  Google Scholar 

  23. Münter S, Sabass B, Selhuber-Unkel C, Kudryashev M, Hegge S, Engel U, Spatz JP, Matuschewski K, Schwarz US, Frischknecht F (2009) Plasmodium sporozoite motility is modulated by the turnover of discrete adhesion sites. Cell Host Microbe 6:551–562

    Article  PubMed  Google Scholar 

  24. Murray CJ, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, Fullman N, Naghavi M, Lozano R, Lopez AD (2012) Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet 379:413–431

    Article  PubMed  Google Scholar 

  25. Oshiro N, Kobayashi C, Iwanaga S, Nozaki M, Namikoshi M, Spring J, Nagai H (2004) A new membrane-attack complex/perforin (MACPF) domain lethal toxin from the nematocyst venom of the Okinawan sea anemone Actineria villosa. Toxicon 43:225–228

    Article  CAS  PubMed  Google Scholar 

  26. Philip N, Orr R, Waters AP (2013) Transfection of rodent malaria parasites. Methods Mol Biol 923:99–125

    Article  CAS  PubMed  Google Scholar 

  27. Pimenta PF, Touray M, Miller L (1994) The journey of malaria sporozoites in the mosquito salivary gland. J Eukaryot Microbiol 41:608–624

    Article  CAS  PubMed  Google Scholar 

  28. Polekhina G, Giddings KS, Tweten RK, Parker MW (2005) Insights into the action of the superfamily of cholesterol-dependent cytolysins from studies of intermedilysin. Proc Natl Acad Sci USA 102:600–605

    Google Scholar 

  29. Ponting CP (1999) Chlamydial homologues of the MACPF (MAC/perforin) domain. Curr Biol 9:R911–913

    Article  CAS  PubMed  Google Scholar 

  30. Raibaud A, Brahimi K, Roth CW, Brey PT, Faust DM (2006) Differential gene expression in the ookinete stage of the malaria parasite Plasmodium berghei. Mol Biochem Parasitol 150:107–113

    Article  CAS  PubMed  Google Scholar 

  31. Roiko MS, Carruthers VB (2013) Functional dissection of toxoplasma gondii perforin-like protein 1 reveals a dual domain mode of membrane binding for cytolysis and parasite egress. J Biol Chem 288:8712–8725

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Rosado CJ, Buckle AM, Law RH, Butcher RE, Kan WT, Bird CH, Ung K, Browne KA, Baran K, Bashtannyk-Puhalovich TA, Faux NG, Wong W, Porter CJ, Pike RN, Ellisdon AM, Pearce MC, Bottomley SP, Emsley J, Smith AI, Rossjohn J, Hartland EL, Voskoboinik I, Trapani JA, Bird PI, Dunstone MA, Whisstock JC (2007) A common fold mediates vertebrate defense and bacterial attack. Science 317:1548–1551

    Article  CAS  PubMed  Google Scholar 

  33. Rosado CJ, Kondos S, Bull TE, Kuiper MJ, Law RH, Buckle AM, Voskoboinik I, Bird PI, Trapani JA, Whisstock JC, Dunstone MA (2008) The MACPF/CDC family of pore-forming toxins. Cell Microbiol 10:1765–1774

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Shahabuddin M, Pimenta PF (1998) Plasmodium gallinaceum preferentially invades vesicular ATPase-expressing cells in Aedes aegypti midgut. Proc Natl Acad Sci USA 95:3385–3389

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Shatursky O, Bayles R, Rogers M, Jost BH, Songer JG, Tweten RK (2000) Clostridium perfringens beta-toxin forms potential-dependent, cation-selective channels in lipid bilayers. Infect Immun 68:5546–5551

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Slade DJ, Lovelace LL, Chruszcz M, Minor W, Lebioda L, Sodetz JM (2008) Crystal structure of the MACPF domain of human complement protein C8 alpha in complex with the C8 gamma subunit. J Mol Biol 379:331–342

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Singh S, Chitnis CE (2012) Signalling mechanisms involved in apical organelle discharge during host cell invasion by apicomplexan parasites. Microbes Infect 14:820–824

    Article  CAS  PubMed  Google Scholar 

  38. Sturm A, Amino R, van de Sand C, Regen T, Retzlaff S, Rennenberg A, Krueger A, Pollok JM, Menard R, Heussler VT (2006) Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids. Science 313:1287–1290

    Article  CAS  PubMed  Google Scholar 

  39. Suarez CE, Noh S (2011) Emerging perspectives in the research of bovine babesiosis and anaplasmosis. Vet Parasitol 180:109–125

    Article  PubMed  Google Scholar 

  40. Tavares J, Formaglio P, Thiberge S, Mordelet E, Van Rooijen N, Medvinsky A, Ménard R, Amino R (2013) Role of host cell traversal by the malaria sporozoite during liver infection. J Exp Med 210:905–915

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Vanderberg JP, Chew S, Stewart MJ (1990) Plasmodium sporozoite interactions with macrophages in vitro: a videomicroscopic analysis. J Protozool 37:528–536

    Article  CAS  PubMed  Google Scholar 

  42. Voskoboinik I, Smyth MJ, Trapani JA (2006) Perforin-mediated target-cell death and immune homeostasis. Nat Rev Immunol 6:940–952

    Article  CAS  PubMed  Google Scholar 

  43. Xu Q, Abdubek P, Astakhova T, Axelrod HL, Bakolitsa C, Cai X, Carlton D, Chen C, Chiu HJ, Clayton T, Das D, Deller MC, Duan L, Ellrott K, Farr CL, Feuerhelm J, Grant JC, Grzechnik A, Han GW, Jaroszewski L, Jin KK, Klock HE, Knuth MW, Kozbial P, Krishna SS, Kumar A, Lam WW, Marciano D, Miller MD, Morse AT, Nigoghossian E, Nopakun A, Okach L, Puckett C, Reyes R, Tien HJ, Trame CB, van den Bedem H, Weekes D, Wooten T, Yeh A, Zhou J, Hodgson KO, Wooley J, Elsliger MA, Deacon AM, Godzik A, Lesley SA, Wilson IA (2010) Structure of a membrane-attack complex/perforin (MACPF) family protein from the human gut symbiont Bacteroides thetaiotaomicron. Acta Crystallogr, Sect F: Struct Biol Cryst Commun 66:1297–1305

    Article  CAS  Google Scholar 

  44. Yeoh S, O’Donnell RA, Koussis K, Dluzewski AR, Ansell KH, Osborne SA, Hackett F, Withers-Martinez C, Mitchell GH, Bannister LH, Bryans JS, Kettleborough CA, Blackman MJ (2007) Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes. Cell 131:1072–1083

    Article  CAS  PubMed  Google Scholar 

  45. Zieler H, Dvorak JA (2000) Invasion in vitro of mosquito midgut cells by the malaria parasite proceeds by a conserved mechanism and results in death of the invaded midgut cells. Proc Natl Acad Sci USA 97:11516–11521

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut Pasteur, Unité de Biologie et Génétique du Paludisme, Département de Parasitologie et Mycologie, 28 rue du Docteur Roux, 75015, Paris, France

    Joana Tavares, Rogerio Amino & Robert Ménard

Authors
  1. Joana Tavares
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rogerio Amino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert Ménard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert Ménard .

Editor information

Editors and Affiliations

  1. National Institute of Chemistry, Ljubljana, Slovenia, Laboratory for Molecular Biology and Nanobiotechnology, Ljubljana, Slovenia

    Gregor Anderluh

  2. Division of Structural Biology, University of Oxford Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom

    Robert Gilbert

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Tavares, J., Amino, R., Ménard, R. (2014). The Role of MACPF Proteins in the Biology of Malaria and Other Apicomplexan Parasites. In: Anderluh, G., Gilbert, R. (eds) MACPF/CDC Proteins - Agents of Defence, Attack and Invasion. Subcellular Biochemistry, vol 80. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8881-6_12

Download citation

Publish with us

Policies and ethics

Search

Navigation