ArticleMolecular biology of the cell2001
Regulated degradation of an endoplasmic reticulum membrane protein in a tubular lysosome in Leishmania mexicana.
Article in Molecular biology of the cell, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 100 citations in OpenAlex.
- TORC1 is an essential regulator of nutrient-controlled proliferation and differentiation in Leishmania.EMBO reports · 2024Article
- Lysosome assembly and disassembly changes endocytosis rate through the Leishmania cell cycle.MicrobiologyOpen · 2020Article
- Article
- Magnesium uptake by connecting fluid-phase endocytosis to an intracellular inorganic cation filter.Nature communications · 2017Article
- Characterization of Leishmania major phosphatidylethanolamine methyltransferases LmjPEM1 and LmjPEM2 and their inhibition by choline analogs.Molecular and biochemical parasitology · 2014Article
- Flavone-resistant Leishmania donovani overexpresses LdMRP2 transporter in the parasite and activates host MRP2 on macrophages to circumvent the flavone-mediated cell death.The Journal of biological chemistry · 2014Article
- Glycosome turnover in Leishmania major is mediated by autophagy.Autophagy · 2014Article
- New insights into roles of acidocalcisomes and contractile vacuole complex in osmoregulation in protists.International review of cell and molecular biology · 2013Review
- Article
- Overexpression of S4D mutant of Leishmania donovani ADF/cofilin impairs flagellum assembly by affecting actin dynamics.Eukaryotic cell · 2012Article
- Morphological events during the cell cycle of Leishmania major.Eukaryotic cell · 2011Article
- Adaptor protein-3 (AP-3) complex mediates the biogenesis of acidocalcisomes and is essential for growth and virulence of Trypanosoma brucei.The Journal of biological chemistry · 2011Article
- Lysosomal degradation of Leishmania hexose and inositol transporters is regulated in a stage-, nutrient- and ubiquitin-dependent manner.International journal for parasitology · 2011Article
- Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.Antimicrobial agents and chemotherapy · 2011Article
- Cryptolepine-Induced Cell Death of Leishmania donovani Promastigotes Is Augmented by Inhibition of Autophagy.Molecular biology international · 2011Article
- Evolution of acidocalcisomes and their role in polyphosphate storage and osmoregulation in eukaryotic microbes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2010Review
- Degradation of host sphingomyelin is essential for Leishmania virulence.PLoS pathogens · 2009Article
- Trypanosome lytic factor, an antimicrobial high-density lipoprotein, ameliorates Leishmania infection.PLoS pathogens · 2009Article
- All Trypanosoma cruzi developmental forms present lysosome-related organelles.Histochemistry and cell biology · 2008Article
- Sitamaquine sensitivity in Leishmania species is not mediated by drug accumulation in acidocalcisomes.Antimicrobial agents and chemotherapy · 2008Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cell surface of the human parasite Leishmania mexicana is coated with glycosylphosphatidylinositol (GPI)-anchored macromolecules and free GPI glycolipids. We have investigated the intracellular trafficking of green fluorescent protein- and hemagglutinin-tagged forms of dolichol-phosphate-mannose synthase (DPMS), a key enzyme in GPI biosynthesis in L. mexicana promastigotes. These functionally active chimeras are found in the same subcompartment of the endoplasmic reticulum (ER) as endogenous DPMS but are degraded as logarithmically growing promastigotes reach stationary phase, coincident with the down-regulation of endogenous DPMS activity and GPI biosynthesis in these cells. We provide evidence that these chimeras are constitutively transported to and degraded in a novel multivesicular tubule (MVT) lysosome. This organelle is a terminal lysosome, which is labeled with the endocytic marker FM 4-64, contains lysosomal cysteine and serine proteases and is disrupted by lysomorphotropic agents. Electron microscopy and subcellular fractionation studies suggest that the DPMS chimeras are transported from the ER to the lumen of the MVT via the Golgi apparatus and a population of 200-nm multivesicular bodies. In contrast, soluble ER proteins are not detectably transported to the MVT lysosome in either log or stationary phase promastigotes. Finally, the increased degradation of the DPMS chimeras in stationary phase promastigotes coincides with an increase in the lytic capacity of the MVT lysosome and changes in the morphology of this organelle. We conclude that lysosomal degradation of DPMS may be important in regulating the cellular levels of this enzyme and the stage-dependent biosynthesis of the major surface glycolipids of these parasites.
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