Calreticulin pp 220-237 | Cite as

Role of Calreticulin in Leishmania Parasite Secretory Pathway and Pathogenesis

  • Alain Debrabant
  • Nancy Lee
  • Dennis M. Dwyer
  • Hira L. Nakhasi
Part of the Molecular Biology Intelligence Unit book series (MBIU)


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.


Visceral Leishmaniasis Parasite Survival Leishmania Donovani Flagellar Pocket Folding Complex 
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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Alain Debrabant
  • Nancy Lee
  • Dennis M. Dwyer
  • Hira L. Nakhasi

There are no affiliations available

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