ArticleProceedings of the National Academy of Sciences of the United States of America2008
Leishmania requires Rab7-mediated degradation of endocytosed hemoglobin for their growth.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 56 citations in OpenAlex.
- Heme and immunity: The heme oxygenase dichotomy.Journal of inorganic biochemistry · 2025Review
- Access and utilization of host-derived iron by Leishmania parasites.Journal of biochemistry · 2023Review
- Neglected Zoonotic Diseases: Advances in the Development of Cell-Penetrating and Antimicrobial Peptides against Leishmaniosis and Chagas Disease.Pathogens (Basel, Switzerland) · 2023Review
- Hemoglobin uptake and utilization by human protozoan parasites: a review.Frontiers in cellular and infection microbiology · 2023Review
- New Insights on Heme Uptake inInternational journal of molecular sciences · 2022Article
- Hemoglobin Endocytosis and Intracellular Trafficking: A Novel Way of Heme Acquisition byPathogens (Basel, Switzerland) · 2022Review
- Evidence that a naturally occurring single nucleotide polymorphism in the RagC gene of Leishmania donovani contributes to reduced virulence.PLoS neglected tropical diseases · 2021Article
- Crystal structure of the GDP-bound GTPase domain of Rab5a from Leishmania donovani.Acta crystallographica. Section F, Structural biology communications · 2020Article
- Leishmania heme uptake involves LmFLVCRb, a novel porphyrin transporter essential for the parasite.Cellular and molecular life sciences : CMLS · 2020Article
- Iron and Heme Metabolism at the Leishmania-Host Interface.Trends in parasitology · 2020Review
- Structural and Biophysical Characterization of Rab5a from Leishmania Donovani.Biophysical journal · 2018Article
- Magnesium uptake by connecting fluid-phase endocytosis to an intracellular inorganic cation filter.Nature communications · 2017Article
- GTPase Sar1 regulates the trafficking and secretion of the virulence factor gp63 inThe Journal of biological chemistry · 2017Article
- Leishmania donovani resides in modified early endosomes by upregulating Rab5a expression via the downregulation of miR-494.PLoS pathogens · 2017Article
- Leishmania major large RAB GTPase is highly immunogenic in individuals immune to cutaneous and visceral leishmaniasis.Parasites & vectors · 2017Article
- Single GDP-dissociation Inhibitor Protein regulates endocytic and secretory pathways in Leishmania.Scientific reports · 2016Article
- Rab5 Isoforms Specifically Regulate Different Modes of Endocytosis in Leishmania.The Journal of biological chemistry · 2016Article
- LmABCB3, an atypical mitochondrial ABC transporter essential for Leishmania major virulence, acts in heme and cytosolic iron/sulfur clusters biogenesis.Parasites & vectors · 2016Article
- Functional Characterization of Monomeric GTPase Rab1 in the Secretory Pathway of Leishmania.The Journal of biological chemistry · 2015Article
- Evolutionary comparison of prenylation pathway in kinetoplastid Leishmania and its sister Leptomonas.BMC evolutionary biology · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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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