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Molecular characterization of transport lectin vesicular integral membrane protein 36 kDa (VIP36) in the life cycle of Schistosoma mansoni

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Abstract

VIP36 is a protein described as an L-type lectin in animals, responsible for the intracellular transport of glycoproteins within the secretory pathway, and also localized on the plasma membrane. Schistosoma mansoni has a complex system of vesicles and protein transport machinery to the cell surface. The excreted/secreted products of the larvae and eggs are known to be exposed to the host immune system. Hence, characterizing the role and action of SmVIP36 in the S. mansoni life cycle is important for a better understanding of the parasite-host relationship. To this purpose, we firstly performed in silico analysis. Analysis of SmVIP36 in silico revealed that it contains a lectin leg-like domain with a jellyroll fold as seen by its putative 3D tertiary structure. Additionally, it was also observed that its CRD contains calcium ion-binding amino acids, suggesting that the binding of SmVIP36 to glycoproteins is calcium-dependent. Finally, we observed that the SmVIP36 predicted amino acid sequence relative to its orthologs was conserved. However, phylogenetic analysis revealed that SmVIP36 follows species evolution, forming a further cluster with its definitive host Homo sapiens. Moreover, q-PCR analysis in the S. mansoni life cycle points to a significant increase in gene expression in the eggs, schistosomulae, and female adult stages. Similarly, protein expression increased in eggs, cercariae, schistosomulae, and adult worm stages. These results suggest that SmVIP36 might participate in the complex secretory activity within the egg envelope and tegument proteins, both important for the stages of the parasite that interact with the host.

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References

  • Arnold K, Bordoli L, Kopp J, Schwede T (2006) The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22(2):195–201

    Article  CAS  PubMed  Google Scholar 

  • Ashton PD, Harrop R, Shah B, Wilson RA (2001) The schistosome egg: development and secretions. Parasitology 122:329–338

    Article  CAS  PubMed  Google Scholar 

  • Berriman M, Haas BJ, Loverde PT, Wilson RA et al (2009) The genome of the blood fluke Schistosoma mansoni. Nature 460(7253):352–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blanton ER, Licate LS (1992) Developmental refulation of protein synthesis in schistosomes. Mol Biochem Parasitol 51(2):201–208

    Article  CAS  PubMed  Google Scholar 

  • Colley DG, Bustinduy AL, Secor WE, King CH (2014) Human schistosomiasis. Lancet 383(9936):2253–2264

    Article  PubMed  PubMed Central  Google Scholar 

  • DeLano WL (2002) The PyMOL molecular graphics system. DeLano Scientific, San Carlos

    Google Scholar 

  • Doenhoff M, Kimani G, Cioli D (2000) Praziquantel and the control of schistosomiasis. Parasitol Today 16(9):364–366

    Article  CAS  PubMed  Google Scholar 

  • Doenhoff MJ, Ciolo D, Utzinger J (2008) Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Curr Opin Infect Dis 21(6):659–667

    Article  CAS  PubMed  Google Scholar 

  • Etzler ME, Surolia A, Cummings RD (2009) L-type Lectins. In: Varki A, Cummings RD, Esko JD et al (eds) Essentials of Glycobiology, 2nd edn. Cold Spring Harbor, New York Chapter 29

    Google Scholar 

  • Fallon PG (1998) Schistosome resistance to praziquantel. Drug Resist Updat 1(4):236–241

    Article  CAS  PubMed  Google Scholar 

  • Fenwick A, Savioli L, Engels D, Bergquist RN, Todd MH (2003) Drugs for the control of parasitic diseases: current status and development in schistosomiasis. Trends Parasitol 19(11):509–515

    Article  CAS  PubMed  Google Scholar 

  • Finn RD, Mistry J, Tate J, Coggill P, Heger A, Pollington JE, Gavin OL, Gunasekaran P, Ceric G, Forslund K, Holm L, Sonnhammer EL, Eddy SR, Bateman A (2009) The Pfam protein families database. Nucleic Acids Res 38:D211–D222

    Article  PubMed  PubMed Central  Google Scholar 

  • Foley M, Kussel JR, Garland PB (1988) Changes in the organization of the surface membrane upon transformation of cercariae to schistosomula of helminth parasite Schistosoma mansoni. Parasitology 96(1):85–97

    Article  PubMed  Google Scholar 

  • Hall N, Karras M, Raine JD, Carlton JM, Kooij TW et al (2005) A comprehensive survey of the Plasmodium life cycle by genomic transcriptomic and proteomic analyses. Science 307(5706):82–86

    Article  CAS  PubMed  Google Scholar 

  • Hara-Kuge S, Ohkura T, Ideo H, Shimada O, Atsumi S, Yamashita K (2002) Involvement of VIP36 in intracellular transport and secretion of glycoproteins in polarized Madin-Darby canine kidney (MDCK) cells. J Biol Chem 277(18):16332–16339

    Article  CAS  PubMed  Google Scholar 

  • Harrop R, Wilson RA (1993) Protein synthesis and release by cultured schistosomula of Schistosoma mansoni. Parasitology 107:265–274

    Article  CAS  PubMed  Google Scholar 

  • Hockley DJ, Mclaren DJ (1973) Schistosoma mansoni: changes in the outer membrane of the tegument during development from cercariae to adult worm. Int J Parasitol 3(1):13–25

    Article  CAS  PubMed  Google Scholar 

  • Hokke CH, Fitzpatrick JM, Hoffmann KF (2007) Integrating transcriptome, proteome, and glycome analyses of Schistosoma biology. Trends Parasitol 23(4):165–174

    Article  CAS  PubMed  Google Scholar 

  • Hotez PJ, Molyneux DH, Fenwick A, Kumaresan J, Sachs SE, Sachs JD, Savioli L (2007) Control of neglected tropical diseases. N Engl J Med 357(10):1018–1027

    Article  CAS  PubMed  Google Scholar 

  • Ismail M, Botros S, Metwally A, William S, Farghally A, Tao LF, Day TA, Bennett JL (1999) Resistance to praziquantel: direct evidence from Schistosoma mansoni isolated from Egyptian villagers. Am J Trop Med Hyg 60(6):932–935

    Article  CAS  PubMed  Google Scholar 

  • Kamiya Y, Yamaguchi Y, Takahashi N, Arata Y, Kasai K, Ihara Y, Matsuo I, Ito Y, Yamamoto K, Kato K (2005) Sugar binding properties of VIP36, an intracellular animal lectin operating as a cargo receptor. J Biol Chem 280(44):37178–37182

    Article  CAS  PubMed  Google Scholar 

  • Kawasaki N, Ichikawa Y, Matsuo I, Totani K, Matsumoto N, Ito Y, Yamamoto K (2008) The sugar-binding ability of ERGIC-53 is enhanced by its interaction with MCFD2. Blood 111(4):1972–1979

    Article  CAS  PubMed  Google Scholar 

  • La D, Esquivel-Rodriguez J, Venkatraman V, Li B, Sael L, Ueng S, Ahrendt S, Kihara D (2009) 3D-SURFER: software for high throughput protein surface comparison and analysis. Bioinformatics 25(21):2843–2844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Laemmli UK (1970) Clevage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(5259):660–885

    Article  Google Scholar 

  • Larkin MA, Blackshields G, Brown NP, Chenna R, Mcgettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23(21):2947–2948

    Article  CAS  PubMed  Google Scholar 

  • Liu F, Lu J, Hu W, Wang SY, Cui SJ, Chi M, Yan Q, Wang XR, Song HD, Xu XN, Wang JJ, Zhang XL, Zhang X, Wang ZQ, Xue CL, Brindley PJ, McManus DP, Yang PY, Feng Z, Chen Z, Han ZG (2006) New perspectives on host-parasite interplay by comparative transcriptomic and proteomic analyses of Schistosoma japonicum. PLoS Pathog 2(4):e29

    Article  PubMed  PubMed Central  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−delta delta C(T)) method. Methods 25(4):402–408

    Article  CAS  PubMed  Google Scholar 

  • Logan-Klumpler FJ, De Silva N, Boehme U, Rogers MB, Velarde G, McQuillan JA, Carver T, Aslett M, Olsen C, Subramanian S, Phan I, Farris C, Mitra S, Ramasamy G, Wang H, Tivey A, Jackson A, Houston R, Parkhill J, Holden M, Harb OS, Brunk BP, Myler PJ, Roos D, Carrington M, Smith DF, Hertz-Fowler C, Berriman M (2012) GeneDB--an annotation database for pathogens. Nucleic Acids Res 40(Database issue):D98–108

    Article  CAS  PubMed  Google Scholar 

  • Machado-Silva JR, Neves RH, Gomes DC (2008) Schistosoma mansoni e esquistossomose: uma visão multidisciplinar. In LENZI (ed) Filogenia, co-evolução, aspectos morfológicos e biológicos das diferentes fases de desenvolvimento do Schistosoma mansoni. 1st edn. Fiocruz, Rio de Janeiro, Chapter 2, pp. 45–84

  • Magnussen P (2003) Treatment and re-treatment strategies for schistosomiasis control in different epidemiological settings: a review of 10 years’ experiences. Acta Trop 86(2–3):243–254

    Article  CAS  PubMed  Google Scholar 

  • McDonald CJ, Jones MK, Wallace DF, Summerville L, Nawaratna S, Subramaniam VN (2010) Increased iron stores correlate with worse disease outcomes in a mouse model of schistosomiasis infection. PLoS One 5(3):1–7

    Google Scholar 

  • Melo TT, Araujo JM, Durães FV, Caliari MV, Oliveira SC, Coelho PMZ, Fonseca CT (2010) Immunization with newly transformed Schistosoma mansoni schistosomula tegument elicits tegument damage, reduction in egg and parasite burden. Parasite Immunol 32(11–12):749–759

    Article  Google Scholar 

  • Mourão MM, Dinguirard N, Franco GR, Yoshino TP (2009) Phenotypic screen of early-developing larvae of the blood fluke, Schistosoma mansoni, using RNA interference. PLoS Negl Trop Dis 3(8):1–13

    Google Scholar 

  • Nagai Y, Gazinelli G, Moraes WG, Pellegrino J (1977) Protein synthesis during cercaria-schistosomulum transformation and early development of the Schistosoma mansoni larvae. Comp Biochem Physiol 57(1):27–30

    CAS  Google Scholar 

  • Ramalho-Pinto FJ, Gazzinelli G, Howells RE, Mota-Santos TA, Figueiredo EA, Pellegrino J (1974) Schistosoma mansoni: defined system for stepwise transformation of cercaria to schistosomule in vitro. Exp Parasitol 36:360–372

    Article  CAS  PubMed  Google Scholar 

  • Rozen S, Skaletsky HJ (2000) Primer3 on the WWW for general users and for biologist programmers. In: Krawetz S, Misener S (eds) Bioinformatics methods and protocols: methods in molecular biology. Humana Press, Totowa, pp 365–386

    Google Scholar 

  • Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4(4):406–425

    CAS  PubMed  Google Scholar 

  • Satoh T, Cowieson NP, Hakamata W, Ideo H, Fukushima K, Kurihara M, Kato R, Yamashita K, Wakatsuki S (2007) Structural basis for recognition of high mannose type glycoproteins by mammalian transport lectin VIP36. J Biol Chem 282(38):28246–28255

    Article  CAS  PubMed  Google Scholar 

  • Shimada O, Hara-Kuge S, Yamashita K, Tosaka-Shimada H, Yanchao L, Einan L, Atsumi S, Ishikawa H (2003) Localization of VIP36 in the post-Golgi secretory pathway also of rat parotid acinar cells. J Histochem Cytochem 51(8):1057–1063

    Article  CAS  PubMed  Google Scholar 

  • Sinha S, Gupta G, Vijayan M, Surolia A (2007) Subunit assembly of plant lectins. Curr Opin Struct Biol 17(5):498–505

    Article  CAS  PubMed  Google Scholar 

  • Skelly PJ, Shoemaker CB (2000) Induction cues for tegument formation during the transformation of Schistosoma mansoni cercarie. Int J Parasitol 30(5):625–631

    Article  CAS  PubMed  Google Scholar 

  • Smithers SR, Terry RJ (1965) The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of the adult worms. Parasitology 55:695–700

    Article  CAS  PubMed  Google Scholar 

  • Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 24(8):1596–1599

    Article  CAS  PubMed  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 76(9):4350–4354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Van Balkom BW, Van Gestel RA, Browers JF, Krigsveld J, Tielens AG, Heck AJ, Van Hellemond JJ (2005) Mass spectrometric analysis of the Schistosoma mansoni tegumental sub-proteome. J Proteome Res 4(3):958–966

    Article  PubMed  Google Scholar 

  • World Health Organization (2013). Schistosomiasis: A major public health problem. [Online] Available from: http://www.who.int/schistosomiasis/en/index.html. Accessed 13 Mar 2013

  • Yoshino TP, Laursen JR (1995) Production of Schistosoma mansoni daughter sporocysts from mother sporocysts maintained in synxenic culture with Biomphalaria glabrata embryonic (Bge) cells. J Parasitol 81(5):714–722

    Article  CAS  PubMed  Google Scholar 

  • Yuckenberg PD, Poupin F, Mansour TE (1987) Schistosoma mansoni: protein composition and synthesis during early development; evidence for early synthesis of heat shock proteins. Exp Parasitol 63(3):301–311

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the Olinda Mara Brigato and Elenice Aparecida de Macedo for technical assistance. Additionally, we are grateful to Dr. Hélio Vannucchi for provision of the q-PCR platform and to Lívia Maria Cordeiro Simões Ambrósio for technical assistance.

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Authors and Affiliations

  1. Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Carlos Chagas Filho Av. 373, Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil

    Alice Maria de M. Ornelas

  2. Department of Biochemistry and Immunology, Medicine School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Renato G. de Paula & Vanderlei Rodrigues

  3. Institute of Genetics and Biochemistry, Federal University of Uberlandia, Campus Patos de Minas, Patos de Minas, Minas Gerais, Brazil

    Enyara R. Morais & Matheus S. Gomes

  4. Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, São Paulo, Brazil

    Lizandra G. Magalhães

  5. Department of Biophysics and Radiobiology, Centre for Biological Sciences, Federal University of Pernambuco, Recife, Pernambuco, Brazil

    Annielle M. B. da Silva

  6. Department of Biological Sciences/Center for Research in Biological Sciences, Institute of Mathematical and Biological Sciences, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil

    William de Castro-Borges

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  1. Alice Maria de M. Ornelas
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  8. Vanderlei Rodrigues
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Correspondence to Alice Maria de M. Ornelas.

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Ethics statement

All experiments involving animals were authorized by the Animal Research Ethics Commission (CETEA) of the University of São Paulo (protocol number n° 078/2012) and complied with the ethical principles in animal research adopted by the Brazilian College of Animal Experimentation (COBEA). The study protocols were in accordance with internationally accepted principles concerning the care and use of laboratory animals.

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The authors are grateful to FAPESP for fellowships and financial support (Processes FAPESP: 2011/04081-0).

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Fig. S1

Predicted amino acid sequence of 308 amino acids of SmVIP36 highlighting lectin leg-like domain. The predicted amino acid sequence was analyzed by using the Pfam algorithm to identify the domain conserved in primary amino acid sequence. The lectin leg-like domain is underlined (GIF 119 kb)

High-resolution image (TIFF 185 kb).

Fig. S2

Transcript amplification of the 133 bp from the SmVIP36 gene and of the 70 bp from the endogenous control GAPDH gene. The primers were designed using the Primer3Plus program and validated by PCR. The samples were analyzed on a 1% agarose gel. 1—molecular weight of 100 bp DNA ladder (Invitrogen), 2—SmVIP36, 3—GAPDH (GIF 72 kb)

High-resolution image (TIFF 113 kb)

ESM 1

3D tertiary structure of SmVIP36 showing their hydrophobic cavities. The three hydrophobic cavities were found using the online software 3D-SURFER and are highlighted in green, blue, and red (MPG 1770 kb)

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Ornelas, A.M.d., de Paula, R.G., Morais, E.R. et al. Molecular characterization of transport lectin vesicular integral membrane protein 36 kDa (VIP36) in the life cycle of Schistosoma mansoni . Parasitol Res 116, 2765–2773 (2017). https://doi.org/10.1007/s00436-017-5587-7

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