The major cell surface glycoprotein procyclin is a receptor for induction of a novel form of cell death in African trypanosomes in vitro

Pearson, Terry W.; Beecroft, Robert P.; Welburn, Susan C.; Ruepp, Stefan; Roditi, Isabel; Hwa, Kuo-Yuan; Englund, Paul T.; Wells, Clive; Murphy, Noel B.

doi:10.1016/s0166-6851(00)00327-3

Cited by 42 publications

(37 citation statements)

References 46 publications

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“…Likewise, similar structures have been reported in cells that undergo autophagy after inhibition of sterol synthesis (Coppens and Courtoy, 1995). Enlarged flagellar pockets and mitochondrial pocket distention have been reported in dying trypanosome cells (Figarella et al, 2005;Lazardi et al, 1990;Pearson et al, 2000;Welburn et al, 1996), although mitochondrial distention might also be due to sensitivity of the trypanosome mitochondrial membrane to lipid perturbation, as has been observed after ergosterol depletion (Coppens and Courtoy, 2000).…”

Section: Vesicular Trafficking Defects and Drmssupporting

confidence: 60%

Sphingolipid synthesis is necessary for kinetoplast segregation and cytokinesis in Trypanosoma brucei

Fridberg

Olson

Nakayasu

et al. 2008

Journal of Cell Science

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Sphingolipids and their metabolites have been thought crucial for cell growth and cell cycle progression, membrane and protein trafficking, signal transduction, and formation of lipid rafts; however, recent studies in trypanosomes point to the dispensability of sphingolipids in some of these processes. In this study, we explore the requirements for de novo sphingolipid biosynthesis in the insect life cycle stage of the African trypanosome Trypanosoma brucei by inhibiting the enzyme serine palmitoyltransferase (SPT2) by using RNA interference or treatment with a potent SPT2 inhibitor myriocin. Mass spectrometry revealed that upon SPT2 inhibition, the parasites contained substantially reduced levels of inositolphosphorylceramide. Although phosphatidylcholine and cholesterol levels were increased to compensate for this loss, the cells were ultimately not viable. The most striking result of sphingolipid reduction in procyclic T. brucei was aberrant cytokinesis, characterized by incomplete cleavage-furrow formation, delayed kinetoplast segregation and emergence of cells with abnormal DNA content. Organelle replication continued despite sphingolipid depletion, indicating that sphingolipids act as second messengers regulating cellular proliferation and completion of cytokinesis. Distention of the mitochondrial membrane, formation of multilamellar structures within the mitochondrion and near the nucleus, accumulation of lipid bodies and, less commonly, disruption of the Golgi complex were observed after prolonged sphingolipid depletion. These findings suggest that some aspects of vesicular trafficking may be compromised. However, flagellar membrane targeting and the association of the flagellar membrane protein calflagin with detergent-resistant membranes were not affected, indicating that the vesicular trafficking defects were mild. Our studies indicate that sphingolipid biosynthesis is vital for cell cycle progression and cell survival, but not essential for the normal trafficking of flagellar membrane-associated proteins or lipid raft formation in procyclic T. brucei.

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Section: Vesicular Trafficking Defects and Drmssupporting

confidence: 60%

Sphingolipid synthesis is necessary for kinetoplast segregation and cytokinesis in Trypanosoma brucei

Fridberg

Olson

Nakayasu

et al. 2008

Journal of Cell Science

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“…Additional evidence supports the role of fly lectins in regulating tsetse fly infections, since it has been shown that the legume lectins ConA, WGA, and Ricinus communis agglutinin have binding affinity for different species of Trypanosoma (75). Moreover, ConA has been shown to induce a novel form of apoptosis among EP-procyclic forms (87), suggesting the presence of a ConA-like lectin in the fly midgut. GPEET procyclics are not recognized by ConA, suggesting that a different lectin, with specificity for Gal or Glc, may recognize the glycan core of the GPI anchor and could control parasite numbers during the earlier stages of infection (71).…”

Section: Bacterial Pathogens the Tick-borne Rickettsial Pathogensmentioning

confidence: 63%

Insight into a Conserved Lifestyle: Protein-Carbohydrate Adhesion Strategies of Vector-Borne Pathogens

Dinglasan

Jacobs-Lorena

2005

Infect Immun

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The incidence of vector-borne diseases such as malaria, dengue, African sleeping sickness, and tick-borne fevers is increasing. Given that current global control efforts have met with limited success, the need to develop novel interventions has become all the more vital. Successful discovery of such interventions is contingent on improving our understanding of how the pathogen interacts with its vertebrate host and also with its invertebrate vector. In this review we examine a premise developed more than 20 years ago (94) that emphasized the role of protein-carbohydrate interactions in microbial pathogenesis, and we present it in the context of vector-pathogen dynamics.Glycans are "essential macromolecules for numerous cellular processes, such as signaling, structural-support, cell-cell interaction, cell-matrix adhesion, growth, protection and trafficking" (94). Their ubiquitous yet tissue-specific occurrence as cell surface glycoconjugates has, over evolutionary time, been exploited by several pathogenic microorganisms as receptors for attachment and invasion (95). While evidence for microbial adherence to mammalian glycolipids and glycoproteins continues to grow (for reviews see references 17, 18, 58, 95, and 115), only recently has evidence for a "protein-carbohydrate recognition strategy" for vector host-pathogen interactions emerged. This review focuses on the most recent advances that describe adherence mechanisms of three different classes of pathogens-bacteria, viruses, and protozoan parasites-to their obligate arthropod vectors. We also discuss how the proteincarbohydrate recognition strategies in both vector and mammalian life stages are apparently conserved and how this conservation could lead to the development of novel strategies for intervention.

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“…23 In T. brucei procyclic forms, similar morphological features of apoptosis could be induced, in vitro, with concanavalin A treatment, 24,25 or under oxidative stress. 26 Additionally, Leishmania amazonensis promastigotes display DNA laddering and chromatin condensation in dense clusters (leading to the breakdown of the nuclear membrane) upon heat-shock, corresponding to classical features of PCD.…”

Section: Introductionmentioning

confidence: 96%

Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis?

2002

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Unicellular organisms, such as the protozoan parasite Leishmania, can be stimulated to show some morphological and biochemical features characteristic of mammalian apoptosis. This study demonstrates that under a variety of stress conditions such as serum deprivation, heat shock and nitric oxide, cell death can be induced leading to genomic DNA fragmentation into oligonucleosomes. DNA fragmentation was observed, without induction, in the infectious stages of the parasite, and correlated with the presence of internucleosomal nuclease activity, visualisation of 45 to 59 kDa nucleases and detection of TUNEL-positive nuclei. DNA fragmentation was not dependent on active effector downstream caspases nor on the lysosomal cathepsin L-like enyzmes CPA and CPB. These data are consistent with the presence of a caspase-independent cell death mechanism in Leishmania, induced by stress and differentiation that differs significantly from metazoa.

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The major cell surface glycoprotein procyclin is a receptor for induction of a novel form of cell death in African trypanosomes in vitro

Cited by 42 publications

References 46 publications

Sphingolipid synthesis is necessary for kinetoplast segregation and cytokinesis in Trypanosoma brucei

Sphingolipid synthesis is necessary for kinetoplast segregation and cytokinesis in Trypanosoma brucei

Insight into a Conserved Lifestyle: Protein-Carbohydrate Adhesion Strategies of Vector-Borne Pathogens

Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis?

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