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Role of Calreticulin in Leishmania Parasite Secretory Pathway and Pathogenesis

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Calreticulin

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

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Abstract

The trypanosomatid parasites Leishmania and Trypanosoma are the causative agents of human diseases such as leishmaniasis, Chagas disease or African sleeping sickness. Some proteins secreted by these protozoan parasites represent virulence factors and contribute to the survival of these pathogen in the human hosts. Therefore, alteration in the secretion of these proteins could result in attenuation of parasite virulence. Calreticulin is an endoplasmic reticulum chaperone protein involved in the quality control of glycoprotein folding in higher eukaryotes. Previously, we isolated and characterized a calreticulin homologue (LdCR) from Leishmania donovani, the causative agent of visceral leishmaniasis. To assess whether modulation of LdCR level in the parasite could affect the release of secretory proteins by Leishmania, we established L. donovani cell lines overexpressing LdCR or its putative N-, P-, or C-domains. In this report, we show that the secretion of secretory acid phosphatase and possibly other proteins trafficking through the secretory pathway of the parasite were affected as a result of overexpression of LdCR P- or C-domain. In addition, parasites expressing either the LdCR N- or P-domain showed significant decrease in survival inside macrophages in vitro. Taken together, these results suggest that disruption of the functions of calreticulin in Leishmania can result in an alteration of the parasite secretory pathway and also reduce its virulence in vitro.

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Authors
  1. Alain Debrabant
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  2. Nancy Lee
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  3. Dennis M. Dwyer
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  4. Hira L. Nakhasi
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Editors and Affiliations

  1. Peninsula Medical School, Devon, U.K. MRC Immunochemistry Unit Department of Biochemistry, University of Oxford, Oxford, UK

    Paul Eggleton Ph.D.

  2. CIHR Membrane Protein Research Group Department of Biochemistry, University of Alberta Edmonton, Alberta, Canada

    Marek Michalak Ph.D.

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Debrabant, A., Lee, N., Dwyer, D.M., Nakhasi, H.L. (2003). Role of Calreticulin in Leishmania Parasite Secretory Pathway and Pathogenesis. In: Eggleton, P., Michalak, M. (eds) Calreticulin. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9258-1_20

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  • DOI: https://doi.org/10.1007/978-1-4419-9258-1_20

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4862-7

  • Online ISBN: 978-1-4419-9258-1

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