Cited by 56Research on Leishmaniasis StudiesCellular transport and secretionTrypanosoma species research and implications

Leishmania requires Rab7-mediated degradation of endocytosed hemoglobin for their growth

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Patel, Nitin, Singh, Sudha B., Basu, Sandip K., Mukhopadhyay, Amitabha·2008·Proceedings of the National Academy of Sciences

Abstract

Leishmania is unable to synthesize heme and must acquire it from exogenous source, the mechanism of which is not known. We have shown that Leishmania endocytoses hemoglobin (Hb) and subsequently degrade it probably to generate heme. To understand how internalized Hb is degraded, we have cloned and expressed Rab7 homolog from Leishmania donovani. Interestingly, Rab7 in Leishmania is found to be localized both on early and late endocytic compartment and regulates both uptake and degradation of endocytosed Hb demonstrating that Rab7 in Leishmania play a very unique role connecting both early and late events of Hb endocytosis. Our data also indicate that overexpression of Rab7:WT in Leishmania induces transport of Hb to lysosomes and rapidly degrade internalized Hb. Whereas Hb transport to lysosomes and its degradation is significantly inhibited in cells overexpressing Rab7:T21N, a GDP locked mutant of Rab7. Moreover, cells overexpressing Rab7:T21N grow at a slower rate (<50%) compared with control Leishmania. Addition of exogenous hemin recovers the growth of Rab7:T21N mutant cells almost to the control level, suggesting that intracellular heme generated by Rab7-mediated Hb degradation is required for optimal growth of the parasites. Thus, our results identify a potential target which might be exploited to suppress the growth of Leishmania.

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Crossref · 10.1073/pnas.0800404105

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  • Leishmania species are unable to synthesize heme by themselves and express receptors for the uptake of HB or heme.

    “In contrast to P. falciparum, Leishmania species, which can cause skin, mucocutaneous or systemic infections, are unable to synthesize heme by themselves and thus express receptors for the uptake of HB or heme, respectively (Krishnamurthy et al., 2005;Patel et al., 2008).”

    From Iron in infection and immunity (2020) · cites this paper as Patel et al., 2008

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Authors
Patel, N., Singh, S. B., Basu, S. K., & Mukhopadhyay, A.
Affiliations
National Institute of Immunology (IN)
Venue
Proceedings of the National Academy of Sciences
Published
2008-03-11
Volume
105
Issue
10
Pages
3980-3985
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2109837906
Cited by
56
References
41
Citations by year
2026: 2 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 1 · 2020: 6 · 2019: 1 · 2018: 3 · 2017: 6 · 2016: 8 · 2015: 4 · 2013: 4 · 2012: 2
FWCI
1.65
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Indo-French Centre for the Promotion of Advanced Research
  • National Institute of Immunology
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
Keywords
Leishmania donovani, Rab7, heme acquisition, lysosomal degradation, parasite growth, antiparasitic drug targets
MeSH terms
rab7 GTP-Binding Proteins, Amino Acid Sequence, Animals, Cell Compartmentation, Cloning, Molecular, Endocytosis, Hemoglobins, Leishmania donovani, Lysosomes, Molecular Sequence Data, Protein Processing, Post-Translational, Sequence Alignment, Sequence Homology, Amino Acid, rab GTP-Binding Proteins, Protein Transport, Mutant Proteins

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