ArticleThe Journal of biological chemistry2016
Rab5 Isoforms Specifically Regulate Different Modes of Endocytosis in Leishmania.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Rab5 nucleotide binding promotes oxidative metabolism to fuel hepatocellular carcinoma cell proliferation.The Journal of biological chemistry · 2026Article
- Drug Repurposing for Kala-Azar.Pharmaceutics · 2025Article
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- Biophysical Evidence for the Amyloid Formation of a Recombinant Rab2 Isoform ofProtein and peptide letters · 2024Article
- 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
- G Protein-Coupled Receptors as Potential Intercellular Communication Mediators in Trypanosomatidae.Frontiers in cellular and infection microbiology · 2022Review
- Crystal structure of the GDP-bound GTPase domain of Rab5a from Leishmania donovani.Acta crystallographica. Section F, Structural biology communications · 2020Article
- Defining the TLT-1 interactome from resting and activated human platelets.Journal of proteomics · 2020Article
- Druggable Targets in Cyclic Nucleotide Signaling Pathways in Apicomplexan Parasites and Kinetoplastids against Disabling Protozoan Diseases in Humans.International journal of molecular sciences · 2019Review
- Small GTPases in platelet membrane trafficking.Platelets · 2019Review
- Article
- Structural and Biophysical Characterization of Rab5a from Leishmania Donovani.Biophysical journal · 2018Article
- Regulation of Rab5 isoforms by transcriptional and post-transcriptional mechanisms in yeast.FEBS letters · 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
- Multifactorial Regulation of G Protein-Coupled Receptor Endocytosis.Biomolecules & therapeutics · 2017Review
- Single GDP-dissociation Inhibitor Protein regulates endocytic and secretory pathways in Leishmania.Scientific reports · 2016Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Differential functions of Rab5 isoforms in endocytosis are not well characterized. Here, we cloned, expressed, and characterized Rab5a and Rab5b from Leishmania and found that both of them are localized in the early endosome. To understand the role of LdRab5 isoforms in different modes of endocytosis in Leishmania, we generated transgenic parasites overexpressing LdRab5a, LdRab5b, or their dominant-positive (LdRab5a:Q93L and LdRab5b:Q80L) or dominant-negative mutants (LdRab5a:N146I and LdRab5b:N133I). Using LdRab5a or its mutants overexpressing parasites, we found that LdRab5a specifically regulates the fluid-phase endocytosis of horseradish peroxidase and also specifically induced the transport of dextran-Texas Red to the lysosomes. In contrast, cells overexpressing LdRab5b or its mutants showed that LdRab5b explicitly controls receptor-mediated endocytosis of hemoglobin, and overexpression of LdRab5b:WT enhanced the transport of internalized Hb to the lysosomes in comparison with control cells. To unequivocally demonstrate the role of Rab5 isoforms in endocytosis in Leishmania, we tried to generate null-mutants of LdRab5a and LdRab5b parasites, but both were lethal indicating their essential functions in parasites. Therefore, we used heterozygous LdRab5a(+/-) and LdRab5b(+/-) cells. LdRab5a(+/-) Leishmania showed 50% inhibition of HRP uptake, but hemoglobin endocytosis was uninterrupted. In contrast, about 50% inhibition of Hb endocytosis was observed in LdRab5b(+/-) cells without any significant effect on HRP uptake. Finally, we tried to identify putative LdRab5a and LdRab5b effectors. We found that LdRab5b interacts with clathrin heavy chain and hemoglobin receptor. However, LdRab5a failed to interact with the clathrin heavy chain, and interaction with hemoglobin receptor was significantly less. Thus, our results showed that LdRab5a and LdRab5b differentially regulate fluid phase and receptor-mediated endocytosis in Leishmania.
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