Skip to main content

Advertisement

SpringerLink
Log in

Caveolins and flotillin-2 are present in the blood stages of Plasmodium vivax

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Blood stages of Plasmodium vivax induce the development of caveolae and caveola–vesicle complexes (CVC) in the membrane of their host erythrocyte. Caveolae are found in almost all types of cells and are involved in endogenous processes as calcium and cholesterol homeostasis, cell signalling, transporting, ligand internalization and transcytosis of serum components. Major structural components of caveolae are the proteins caveolins and flotillins. The functional role of caveolae in the P. vivax-infected erythrocyte is not properly understood. As these organelles have been shown to contain malaria antigens, it has been suggested that they are involved in the transport and release of specific parasite antigens from the infected erythrocyte and in the uptake of plasma proteins. Using specific antibodies to classical caveolae proteins and an immunolocalization approach, we found caveolin-2, caveolin-3, and flotillin-2 in the vesicle profiles and some CVC of P. vivax-infected erythrocytes. Caveolin-1–3 were not found in uninfected erythrocytes. This is the first report of identification and localization of caveolins in the CVC present in erythrocytes infected with P. vivax, thereby providing evidence of the role of this particular organelle in the protein-trafficking pathway that connect parasite-encoded proteins with the erythrocyte cytoplasm and the cell surface throughout the asexual blood cycle of vivax malaria parasite.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Adisa A, Rug M, Klonis N, Foley M, Cowman AF, Tilley L (2002) The signal sequence of exported protein-1 directs the green fluorescent protein to the parasitophorous vacuole of transfected malaria parasites. J Biol Chem 278:6532–6542

    Article  PubMed  Google Scholar 

  • Aikawa M, Atkinson CT (1990) Immunoelectron microscopy of parasites. Adv Parasitol 29:151–214

    Article  PubMed  CAS  Google Scholar 

  • Aikawa M, Miller LH, Rabbege J (1975) Caveola-vesicle complexes in the plasmalemma of erythrocytes infected by Plasmodium vivax and P. cynomolgi. Am J Pathol 79:285–294

    PubMed  CAS  Google Scholar 

  • Andrysiak PM, Collins WE, Campbell GH (1986) Concentration of Plasmodium ovale and Plasmodium vivax-infected erythrocytes from non-human primate blood using Percoll gradients. Am J Trop Med Hyg 35:251–254

    PubMed  CAS  Google Scholar 

  • Atkinson CT, Aikawa M (1990) Ultrastructure of malaria-infected erythrocytes. Blood Cells 16:351–368

    PubMed  CAS  Google Scholar 

  • Barnwell JW (1990) Vesicle-mediated transport of membrane and proteins in malaria-infected erythrocytes. Blood Cells 16:379–395

    PubMed  CAS  Google Scholar 

  • Barnwell JW, Ingravallo P, Galinski MR, Matsumoto Y, Aikawa M (1990) Plasmodium vivax: malarial proteins associated with the membrane-bound caveola–vesicle complexes and cytoplasmic cleft structures of infected erythrocytes. Exp Parasitol 70:85–99

    Article  PubMed  CAS  Google Scholar 

  • Behari R, Haldar K (1994) Plasmodium falciparum: protein localization along a novel, lipid-rich tubovesicular membrane network in infected erythrocytes. Exp Parasitol 79:250–259

    Article  PubMed  CAS  Google Scholar 

  • Bender F, Montoya M, Monardes V, Leyton L, Quest AF (2002) Caveolae and caveolae-like membrane domains in cellular signaling and disease: identification of downstream targets for the tumor suppressor protein caveolin-1. Biol Res 35:151–167

    Article  PubMed  CAS  Google Scholar 

  • Bickel PE, Scherer PE, Schnitzer JE, Oh P, Lisanti MP, Lodish HF (1997) Flotillin and epidermal surface antigen define a new family of caveolae-associated integral membrane proteins. J Biol Chem 272:13793–13802

    Article  PubMed  CAS  Google Scholar 

  • Bracho C, Dunia I, Romano M, Benedetti EL, Perez HA (2001) Plasmodium vivax and Plasmodium chabaudi: intraerythrocytic traffic of homologous proteins involves a Brefeldin A-sensitive secretory pathway. Eur J Cell Biol 80:164–170

    Article  PubMed  CAS  Google Scholar 

  • Bracho C, Dunia I, De La Rosa M, Benedetti EL, Perez HA (2002) Traffic pathways of Plasmodium vivax antigens during intraerythrocytic development. Parasitol Res 88:253–258

    Article  PubMed  Google Scholar 

  • Brazer SW, Singh BB, Liu X, Swaim W, Ambudkar IS (2003) Caveolin-1 contributes to assembly of store-operated Ca2+ influx channels by regulating plasma membrane localization of TRPC1. J Biol Chem 278:27208–27215

    Article  PubMed  CAS  Google Scholar 

  • Edgar AJ, Polak JM (2001) Flotillin-1: gene structure: cDNA cloning from human lung and the identification of alternative polyadenylation signals. Int J Biochem Cell Biol 33:53–64

    Article  PubMed  CAS  Google Scholar 

  • Elmendorf HG, Haldar K (1993) Secretory transport in Plasmodium. Parasitol Today 9:98–102

    Article  PubMed  CAS  Google Scholar 

  • Field MC, Gabernet-Castello C, Dacks JB (2006) Reconstructing the evolution of the endocytic system: insights from genomics and molecular cell biology. In: Jékely G (ed) Origin and evolution of eukaryotic endomembranes and cytoskeleton. Taylor and Francis Group, Oxford, pp 1–13

    Google Scholar 

  • Fujioka H, Torii M, Barnwell JW, Aikawa M (1992) Localization of F-actin on the caveola-vesicle complex of the erythrocytes infected with Plasmodium vivax and Plasmodium cynomolgi. Jpn J Parasitol 41:361–364

    Google Scholar 

  • Hiller NL, Akompong T, Morrow JS, Holder AA, Haldar K (2003) Identification of a stomatin orthologue in vacuoles induced in human erythrocytes by malaria parasites. A role for microbial raft proteins in apicomplexan vacuole biogenesis. J Biol Chem 278:48413–48421

    Article  PubMed  CAS  Google Scholar 

  • Ihalamulla RL, Mendis KN (1987) Plasmodium vivax: isolation of mature asexual stages and gametocytes from infected human blood by colloidal silica (Percoll) gradient centrifugation. Trans R Soc Trop Med Hyg 81:25–28

    Article  PubMed  CAS  Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  PubMed  CAS  Google Scholar 

  • Lauer S, VanWye J, Harrison T, McManus H, Samuel BU, Hiller NL, Mohandas N, Haldar K (2000) Vacuolar uptake of host components, and a role for cholesterol and sphingomyelin in malarial infection. EMBO J 19:3556–3564

    Article  PubMed  CAS  Google Scholar 

  • Lee H, Park DS, Wang XB, Scherer PE, Schwartz PE, Lisanti MP (2002) Src-induced phosphorylation of caveolin-2 on tyrosine 19. J Biol Chem 277:34556–34567

    Article  PubMed  CAS  Google Scholar 

  • Monier S, Parton RG, Vogel F, Behlke J, Henske A, Kurzchalia TV (1995) VIP21-caveolin, a membrane protein constituent of the caveolar coat, oligomerizes in vivo and in vitro. Mol Biol Cell 6:911–927

    PubMed  CAS  Google Scholar 

  • Monier S, Dietzen DJ, Hastings WR, Lublin DM, Kurzchalia TV (1996) Oligomerization of VIP21-caveolin in vitro is stabilized by long chain fatty acylation or cholesterol. FEBS Lett 388:143–149

    Article  PubMed  CAS  Google Scholar 

  • Murata M, Peranen J, Schreiner R, Wieland F, Kurzchalia TV, Simons K (1995) VIP21/caveolin is a cholesterol-binding protein. Proc Natl Acad Sci U S A 92:10339–10343

    Article  PubMed  CAS  Google Scholar 

  • Murphy SC, Samuel BU, Harrison T, Speicher KD, Speicher DW, Reid ME, Prohaska R, Low PS, Tanner MJ, Mohandas N, Haldar K (2003) Erythrocyte detergent-resistant membrane proteins: their characterization and selective uptake during malarial infection. Blood 103:1920–1928

    Article  PubMed  CAS  Google Scholar 

  • Nagao E, Seydel KB, Dvorak JA (2002) Detergent-resistant erythrocyte membrane rafts are modified by a Plasmodium falcuparum infection. Exp Parasitol 102:57–59

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Parton RG (1996) Caveolae and caveolins. Curr Opin Cell Biol 8:542–548

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Perez HA, Wide A, Bracho C, De La Rosa M (1995) Plasmodium vivax: detection of blood parasites using fluorochrome labelled monoclonal antibodies. Parasite Immunol 17:305–312

    Article  PubMed  CAS  Google Scholar 

  • Perez HA, Bracho C, Romano M, De La Rosa M (1997) Plasmodium vivax and Plasmodium chabaudi: interspecies cross-reacting antigens. Parasitol Res 83:246–251

    Article  PubMed  CAS  Google Scholar 

  • Raposo G, Kleijmeer MJ, Posthuma G, Slot JW, Geuze HJ (1997) Immunogold labeling of ultrathin cryosections: application in immunology. Handbook of Exp Immunol 5th edn., vol. 4. Blackwell Science, Cambridge, Massachusetts, pp 1–11

    Google Scholar 

  • Reynolds ES (1963) The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol 17:208–212

    Article  PubMed  CAS  Google Scholar 

  • Richards W, Williams G (1973) The removal of leukocytes from malaria infected blood. Ann Trop Med Parasitol 67:249–250

    PubMed  CAS  Google Scholar 

  • Salzer U, Prohaska R (2001) Stomatin, flotillin-1, and flotillin-2 are major integral proteins of erythrocyte lipid rafts. Blood 97:1141–1143

    Article  PubMed  CAS  Google Scholar 

  • Salzer U, Hinterdorfer P, Hunger U, Borken C, Prohaska R (2002) Ca++-dependent vesicle release from erythrocytes involves stomatin-specific lipid rafts, synexin (annexin VII), and sorcin. Blood 99:2569–2577

    Article  PubMed  CAS  Google Scholar 

  • Sando GN, Zhu H, Weis JM, Richman JT, Wertz PW, Madison KC (2003) Caveolin expression and localization in human keratinocytes suggest a role in lamellar granule biogenesis. J Invest Dermatol 120:531–541

    Article  PubMed  CAS  Google Scholar 

  • Sargiacomo M, Scherer PE, Tang Z, Kubler E, Song KS, Sanders MC, Lisanti MP (1995) Oligomeric structure of caveolin: implications for caveolae membrane organization. Proc Natl Acad Sci U S A 92:9407–9411

    Article  PubMed  CAS  Google Scholar 

  • Sharma DK, Choudhury A, Singh RD, Wheatley CL, Marks DL, Pagano RE (2003) Glycosphingolipids internalized via caveolar-related endocytosis rapidly merge with the clathrin pathway in early endosomes and form microdomains for recycling. J Biol Chem 278:7564–7572

    Article  PubMed  CAS  Google Scholar 

  • Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 74:4350–4354

    Article  Google Scholar 

  • Trelka DP, Schneider TG, Reeder JC, Taraschi TF (2000) Evidence for vesicle-mediated trafficking of parasite proteins to the host cell cytosol and erythrocyte surface membrane in Plasmodium falciparum infected erythrocytes. Mol Biochem Parasitol 106:131–145

    Article  PubMed  CAS  Google Scholar 

  • Udagama PV, Atkinson CT, Peiris JSM, David PH, Mendis KN, Aikawa M (1988) Immunoelectron microscopy of Schüffner’s dots in Plasmodium vivax-infected human erythrocytes. Am J Pathol 131:48–52

    PubMed  CAS  Google Scholar 

  • Volonte D, Galbiati F, Li S, Nishiyama K, Okamoto T, Lisanti MP (1999) Flotillins/cavatellins are differentially expressed in cells and tissues and form a hetero-oligomeric complex with caveolins in vivo. Characterization and epitope-mapping of a novel flotillin-1 monoclonal antibody probe. J Biol Chem 274:12702–12709

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Thanks to the personnel of the Malaria Diagnostic Centres sponsored by the Ministry of Health and Social Development in Puerto Ayacucho, Amazonas State (Zone XX) and Caracas (Zone X) for the valuable help with the field collection of human blood samples infected with P. vivax. This research received financial support from FONACIT (grants S1-2000000633 and F-2000001531), the “Centre National de la Recherche Scientific” (CNRS, France), and ECOS-NORD-FONACIT (Grant V04S02-PI-2003000313). We assure that the experiments presented in this paper comply with the current laws of Venezuela and France.

Author information

Authors and Affiliations

  1. Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Microbiología y Biología Celular, Apdo. 21827, Caracas, 1020A, Venezuela

    Carmen Bracho, Mirtha Romano, Mercedes De La Rosa & Hilda A. Pérez

  2. Institut J. Monod, CNRS-Université Paris 6-7, 2, Place Jussieu, 75251, Paris, Cedex 05, France

    Irene Dunia & Ennio-Lucio Benedetti

  3. Institut Curie, CNRS UMR 144, 75248, Paris, Cedex 05, France

    Graça Raposo

Authors
  1. Carmen Bracho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Irene Dunia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mirtha Romano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Graça Raposo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mercedes De La Rosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ennio-Lucio Benedetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hilda A. Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carmen Bracho.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bracho, C., Dunia, I., Romano, M. et al. Caveolins and flotillin-2 are present in the blood stages of Plasmodium vivax . Parasitol Res 99, 153–159 (2006). https://doi.org/10.1007/s00436-006-0139-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-006-0139-6

Keywords

Search

Navigation