Skip to main content Accessibility help

Molecular characterization and transcriptional analysis of the female-enriched chondroitin proteoglycan 2 of Toxocara canis

  • G.X. Ma (a1) (a2), R.Q. Zhou (a1), L. Hu (a1), Y.L. Luo (a1), Y.F. Luo (a1) and H.H. Zhu (a1)...


Toxocara canis is an important but neglected zoonotic parasite, and is the causative agent of human toxocariasis. Chondroitin proteoglycans are biological macromolecules, widely distributed in extracellular matrices, with a great diversity of functions in mammals. However, there is limited information regarding chondroitin proteoglycans in nematode parasites. In the present study, a female-enriched chondroitin proteoglycan 2 gene of T. canis (Tc-cpg-2) was cloned and characterized. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure the transcription levels of Tc-cpg-2 among tissues of male and female adult worms. A 485-amino-acid (aa) polypeptide was predicted from a continuous 1458-nuleotide open reading frame and designated as TcCPG2, which contains a 21-aa signal peptide. Conserved domain searching indicated three chitin-binding peritrophin-A (CBM_14) domains in the amino acid sequence of TcCPG2. Multiple alignment with the inferred amino acid sequences of Caenorhabditis elegans and Ascaris suum showed that CBM_14 domains were well conserved among these species. Phylogenetic analysis suggested that TcCPG2 was closely related to the sequence of chondroitin proteoglycan 2 of A. suum. Interestingly, a high level of Tc-cpg-2 was detected in female germline tissues, particularly in the oviduct, suggesting potential roles of this gene in reproduction (e.g. oogenesis and embryogenesis) of adult T. canis. The functional roles of Tc-cpg-2 in reproduction and development in this parasite and related parasitic nematodes warrant further functional studies.


Corresponding author


Hide All
Achur, R.N., Kakizaki, I., Goel, S., Kojima, K., Madhunapantula, S.V., Goyal, A., Ohta, M., Kumar, S., Takagaki, K. & Gowda, D.C. (2008) Structural interactions in chondroitin 4-sulfate mediated adherence of Plasmodium falciparum infected erythrocytes in human placenta during pregnancy-associated malaria. Biochemistry 47, 1263512643.
Archelli, S., Santillan, G.I., Fonrouge, R., Céspedes, G., Burgos, L. & Radman, N. (2014) Toxocariasis: seroprevalence in abandoned-institutionalized children and infants. Revista Argentina De Microbiología 46, 36.
Boag, P.R., Gasser, R.B., Nisbet, A.J. & Newton, S.E. (2003) Genomics of reproduction in parasitic nematodes – fundamental and biotechnological implications. Biotechnology Advances 21, 103108.
Camaioni, A., Salustri, A., Yanagishita, M. & Hascall, V.C. (1996) Proteoglycans and proteins in the extracellular matrix of mouse cumulus cell–oocyte complexes. Archives of Biochemistry and Biophysics 325, 190198.
Cong, W., Meng, Q.F., You, H.L., Zhou, N., Dong, X.Y., Dong, W., Wang, X.Y., Qian, A.D. & Zhu, X.Q. (2015) Seroprevalence and risk factors of Toxocara infection among children in Shandong and Jilin provinces, China. Acta Tropica 152, 215219.
Dyck, S.M. & Karimi-Abdolrezaee, S. (2015) Chondroitin sulfate proteoglycans: key modulators in the developing and pathologic central nervous system. Experimental Neurology 269, 169187.
Edgar, R.C. (2004) MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5, 113.
Frick, I.M., Schmidtchen, A. & Sjöbring, U. (2003) Interactions between M proteins of Streptococcus pyogenes and glycosaminoglycans promote bacterial adhesion to host cells. European Journal of Biochemistry 270, 23032311.
Fthenou, E., Zafiropoulos, A., Tsatsakis, A., Stathopoulos, A., Karamanos, N.K. & Tzanakakis, G.N. (2006) Chondroitin sulfate A chains enhance platelet derived growth factor-mediated signalling in fibrosarcoma cells. International Journal of Biochemistry & Cell Biology 38, 21412150.
Gallagher, J.T. (1989) The extended family of proteoglycans: social residents of the pericellular zone. Current Opinion in Cell Biology 1, 12011218.
Gamain, B., Gratepanche, S., Miller, L.H. & Baruch, D.I. (2002) Molecular basis for the dichotomy in Plasmodium falciparum adhesion to CD36 and chondroitin sulfate A. Proceedings of the National Academy of Sciences, USA 99, 1002010024.
Gasser, R.B., Korhonen, P.K., Zhu, X.Q. & Young, N.D. (2016) Harnessing the Toxocara genome to underpin toxocariasis research and new interventions. Advances in Parasitology 91, 87110.
Gubbiotti, M.A. & Iozzo, R.V. (2015) Proteoglycans regulate autophagy via outside-in signaling: an emerging new concept. Matrix Biology 48, 613.
Hardingham, T. & Bayliss, M. (1990) Proteoglycans of articular cartilage changes in aging and in joint disease. Seminars in Arthritis and Rheumatism 20, 1233.
Hardingham, T.E. & Fosang, A.J. (1992) Proteoglycans: many forms and many functions. FASEB Journal 6, 861870.
Holland, C.V. (2015) Knowledge gaps in the epidemiology of Toxocara: the enigma remains. Parasitology 16, 114.
Hwang, H.Y. & Horvitz, H.R. (2002) The SQV-1 UDP-glucuronic acid decarboxylase and the SQV-7 nucleotide–sugar transporter may act in the Golgi apparatus to affect Caenorhabditis elegans vulval morphogenesis and embryonic development. Proceedings of the National Academy of Sciences, USA 99, 1421814223.
Hwang, H.Y., Olsen, S.K., Esko, J.D. & Horvitz, H.R. (2003) Caenorhabditis elegans early embryogenesis and vulval morphogenesis depend on chondroitin biosynthesis. Nature 423, 439443.
Im, A.R., Kim, J.Y., Kim, H.S., Cho, S., Park, Y. & Kim, Y.S. (2013) Wound healing and antibacterial activities of chondroitin sulfate- and acharan sulfate-reduced silver nanoparticles. Nanotechnology 24, 395102.
Iozzo, R.V. (1998) Matrix proteoglycans: from molecular design to cellular function. Annual Review of Biochemistry 67, 609652.
Izumikawa, T., Kitagawa, H., Mizuguchi, S., Nomura, K.H., Nomura, K., Tamura, J., Gengyo-Ando, K., Mitani, S. & Sugahara, K. (2004) Nematode chondroitin polymerizing factor showing cell-/organ-specific expression is indispensable for chondroitin synthesis and embryonic cell division. Journal of Biological Chemistry 279, 5375553761.
Johnston, W.L., Krizus, A. & Dennis, J.W. (2006) The eggshell is required for meiotic fidelity, polar-body extrusion and polarization of the C . elegans embryo. BMC Biology 4, 35.
Katoh, K. & Standley, D.M. (2013) MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Molecular Biology and Evolution 30, 772780.
Kwok, J.C., Dick, G., Wang, D. & Fawcett, J.W. (2011) Extracellular matrix and perineuronal nets in CNS repair. Developmental Neurobiology 71, 10731089.
Laabs, T.L., Wang, H., Katagiri, Y., McCann, T., Fawcett, J.W. & Geller, H.M. (2007) Inhibiting glycosaminoglycan chain polymerization decreases the inhibitory activity of astrocyte-derived chondroitin sulfate proteoglycans. Journal of Neuroscience 27, 1449414501.
Lalitha, S. (2004) Primer Premier 5. Biotechnology Software & Internet Journal 1, 270272.
Lee, R.M., Moore, L.B., Bottazzi, M.E. & Hotez, P.J. (2014) Toxocariasis in North America: a systematic review. PLoS Neglected Tropical Diseases 8, e3116.
Marchler-Bauer, A., Derbyshire, M.K., Gonzales, N.R., Lu, S., Chitsaz, F., Geer, L.Y., Geer, R.C., He, J., Gwadz, M., Hurwitz, D.I., Lanczycki, C.J., Lu, F., Marchler, G.H., Song, J.S., Thanki, N., Wang, Z., Yamashita, R.A., Zhang, D., Zheng, C. & Bryant, S.H. (2015) CDD: NCBI's conserved domain database. Nucleic Acids Research 43, D222–226.
Mardberg, K., Trybala, E., Tufaro, F. & Bergström, T. (2002) Herpes simplex virus type 1 glycoprotein C is necessary for efficient infection of chondroitin sulfate-expressing gro2C cells. Journal of General Virology 83, 291300.
Miller, G.M. & Hsieh-Wilson, L.C. (2015) Sugar-dependent modulation of neuronal development, regeneration, and plasticity by chondroitin sulfate proteoglycans. Experimental Neurology 274, 115125.
Mizuguchi, S., Uyama, T., Kitagawa, H., Nomura, K.H., Dejima, K., Gengyo-Ando, K., Mitani, S., Sugahara, K. & Nomura, K. (2003) Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans . Nature 423, 443448.
Morgenstern, D.A., Asher, R.A. & Fawcett, J.W. (2002) Chondroitin sulphate proteoglycans in the CNS injury response. Progress in Brain Research 137, 313332.
Nisbet, A.J., Cottee, P.A. & Gasser, R.B. (2004) Molecular biology of reproduction and development in parasitic nematodes: progress and opportunities. International Journal for Parasitology 34, 125138.
Nisbet, A.J., Cottee, P.A. & Gasser, R.B. (2008) Genomics of reproduction in nematodes: prospects for parasite intervention? Trends in Parasitology 24, 8995.
Olson, S.K., Bishop, J.R., Yates, J.R., Oegema, K. & Esko, J.D. (2006) Identification of novel chondroitin proteoglycans in Caenorhabditis elegans: embryonic cell division depends on CPG-1 and CPG-2. Journal of Cell Biology 173, 985994.
Othman, A.A. (2012) Therapeutic battle against larval toxocariasis: are we still far behind? Acta Tropica 124, 171178.
Overgaauw, P.A. & van Knapen, F. (2013) Veterinary and public health aspects of Toxocara spp. Veterinary Parasitology 193, 398403.
Petersen, T.N., Brunak, S., von Heijne, G. & Nielsen, H. (2011) SignalP 4.0: discriminating signal peptides from transmembrane regions. Nature Methods 8, 785786.
Poulsen, C.S., Skov, S., Yoshida, A., Skallerup, P., Maruyama, H., Thamsborg, S.M. & Nejsum, P. (2015) Differential serodiagnostics of Toxocara canis and Toxocara cati – is it possible? Parasite Immunology 37, 204207.
Pradel, G., Garapaty, S. & Frevert, U. (2002) Proteoglycans mediate malaria sporozoite targeting to the liver. Molecular Microbiology 45, 637651.
Roy, A., Kucukura, A. & Zhang, Y. (2010) I-TASSER: a unified platform for automated protein structure and function prediction. Nature Protocols 5, 725738.
Rubinsky-Elefant, G., Hirata, C.E., Yamamoto, J.H. & Ferreira, M.U. (2010) Human toxocariasis: diagnosis, worldwide seroprevalences and clinical expression of the systemic and ocular forms. Annals of Tropical Medicine and Parasitology 104, 323.
Ruoslahti, E. (1988) Structure and biology of proteoglycans. Annual Review of Cell Biology 4, 229255.
Sahu, S., Samanta, S., Sudhakar, N.R., Raina, O.K., Gupta, S.C., Maurya, P.S., Pawde, A.M. & Kumar, A. (2014) Prevalence of canine toxocariasis in Bareilly, Uttar Pradesh, India. Journal of Parasitic Diseases 38, 111115.
Sato, M., Grant, B.D., Harada, A. & Sato, K. (2008) Rab11 is required for synchronous secretion of chondroitin proteoglycans after fertilization in Caenorhabditis elegans . Journal of Cell Science 121, 31773186.
Schaefer, L. (2014) Proteoglycans, key regulators of cell-matrix dynamics. Matrix Biology 35, 12.
Schaefer, L. & Schaefer, R.M. (2010) Proteoglycans: from structural compounds to signaling molecules. Cell and Tissue Research 339, 237246.
Sievers, F., Wilm, A., Dineen, D., Gibson, T.J., Karplus, K., Li, W., Lopez, R., McWilliam, H., Remmert, M., Söding, J., Thompson, J.D. & Higgins, D.G. (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Molecular Systems Biology 7, 539.
Strube, C., Heuer, L. & Janecek, E. (2013) Toxocara spp. infections in paratenic hosts. Veterinary Parasitology 193, 375389.
Urquhart, G.M., Armour, J., Duncan, J.L., Dunn, A.M. & Jennings, F.W. (2003) Veterinary parasitology. Scotland, Blackwell Science.
Whitten, S.J. & Miller, M.A. (2007) The role of gap junctions in Caenorhabditis elegans oocyte maturation and fertilization. Developmental Biology 301, 432446.
Yang, J., Yan, R., Roy, A., Xu, D., Poisson, J. & Zhang, Y. (2015) The I-TASSER Suite: protein structure and function prediction. Nature Methods 12, 78.
Yi, J.H., Katagiri, Y., Susarla, B., Figge, D., Symes, A.J. & Geller, H.M. (2012) Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice. Journal of Comparative Neurology 520, 32953313.
Zhou, R.Q., Ma, G.X., Korhonen, P.K., Luo, Y.-L., Zhu, H.H., Luo, Y.-F., Gasser, R.B. & Xia, Q.Y. (2017) Comparative transcriptomic analyses of male and female adult Toxocara canis . Gene 600, 8589.
Zhu, X.Q., Korhonen, P.K., Cai, H., Young, N.D., Nejsum, P., von Samson-Himmelstjerna, G., Boag, P.R., Tan, P., Li, Q., Min, J., Yang, Y., Wang, X., Fang, X., Hall, R.S., Hofmann, A., Sternberg, P.W., Jex, A.R. & Gasser, R.B. (2015) Genetic blueprint of the zoonotic pathogen Toxocara canis . Nature Communications 6, 6145.


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed