Lipid homeostasis is essential to the maintenance of life. We previously reported that disruptions of the parasite Na homeostasis via inhibition of PfATP4 resulted in elevated cholesterol within the parasite plasma membrane as assessed by saponin sensitivity. A large number of compounds have been shown to target the parasite Na homeostasis. We screened 800 compounds from the Malaria and Pathogen Boxes to identify chemotypes that disrupted the parasite plasma membrane lipid homeostasis. Here, we show that the compounds disrupting parasite Na homeostasis also induced saponin sensitivity, an indication of parasite lipid homeostasis disruption. Remarkably, 13 compounds were identified that altered the plasma membrane lipid composition independently of the Na homeostasis disruption. Further studies suggest that these compounds target the Plasmodium falciparum Niemann-Pick type C1-related (PfNCR1) protein, which is hypothesized to be involved in maintaining plasma membrane lipid composition. PfNCR1, like PfATP4, appears to be targeted by multiple chemotypes with the potential for drug discovery.
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http://dx.doi.org/10.1021/acsinfecdis.8b00277 | DOI Listing |
Parasitol Res
December 2024
Institute of Hygiene and Microbiology, University of Würzburg, Josef-Schneider-Strasse 2, 97080, Würzburg, Germany.
Pluripotent somatic stem cells are the drivers of unlimited growth of Echinococcus multilocularis metacestode tissue within the organs of the intermediate host. To understand the dynamics of parasite proliferation within the host, it is therefore important to delineate basic mechanisms of Echinococcus stem cell maintenance and differentiation. We herein undertake the first step towards characterizing the role of an evolutionarily old metazoan cell-cell communication system, delta/notch signalling, in Echinococcus cell fate decisions.
View Article and Find Full Text PDFChembiochem
December 2024
Illinois State University, Chemistry, UNITED STATES OF AMERICA.
Protein degradation is pivotal for all biochemical aspects of cellular function. In mammalian cells, protein degradation is mediated mainly by the ubiquitin proteasome system (UPS) and the autophagic-lysosomal system (ALS). Over the last two decades, different types of targeted protein degradation approaches have been developed including proteolysis targeting chimeras (PROTACs) and lysosome targeting chimeras (LYTACs), which employ the UPS to degrade intracellular proteins and the ALS to degrade extracellular and membrane proteins respectively.
View Article and Find Full Text PDFPlant Cell Rep
December 2024
School of Horticulture and Landscape Architecture, Henan Institute of Science and Technology, Xinxiang, 453003, China.
BrSWEET11 accelerated Arabidopsis thaliana flowering, while silencing Brsweet11 in Brassica rapa delayed flowering relative to controls. BrSWEET11 is involved in sucrose transport after being induced by long-day conditions. SWEETs (Sugars Will Eventually Be Exported Transporters) are sugar outflow transporters that may participate in the regulation of plant flowering.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
December 2024
Institute of Physiology, University Duisburg-Essen, Essen, Germany.
Over the last few decades, the primary cilium, an inconspicuous cell organelle, has increasingly become the focus of current research. The primary cilium is a microtubule-based, non-motile, antenna-like structure that is present on almost all mammalian cells. The ciliary membrane incorporates a large number of receptor molecules, which further characterize this cellular organelle.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Ecole Normale Supérieure, Department of Chemistry, 24, rue Lhomond, 75005, Paris, FRANCE.
Giant unilamellar vesicles (GUVs) are widely used minimal cell models where essential biological features can be reproduced, isolated and studied. Although precise spatio-temporal distribution of membrane domains is a process of crucial importance in living cells, it is still highly challenging to generate anisotropic GUVs with domains at user-defined positions. Here we describe a novel and robust method to control the spatial position of lipid domains of liquid-ordered (Lo) / liquid-disordered (Ld) phase in giant unilamellar vesicles (GUVs).
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