STK35L1 regulates host cell cycle-related genes and is essential for Plasmodium infection during the liver stage of malaria

Sharma, Phulwanti Kumari; Kalia, Inderjeet; Kaushik, Vibha; Brünnert, Daniela; Quadiri, Afshana; Kashif, Mohammad; Chahar, Kirti Raj; Agrawal, Akhil; Singh, Agam Prasad; Goyal, Pankaj

doi:10.1016/j.yexcr.2021.112764

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…Oligos were cleaved and collected from ROIs using the GeoMx Digital Spatial Profiler for quantification. We observed host proteins/post-translational modifications that were both up-and down-regulated in infected regions compared to uninfected mice (Figure 1C), some of which have been previously identified as altered upon, or important for, infection (Table S1A) (Kaushansky et al, 2013a;Kaushansky et al, 2013b;Douglass et al, 2015;Boonhok et al, 2016;Arang et al, 2017;Glennon et al, 2019;Sharma et al, 2021). Because we conducted multiple DSP runs with tissues on multiple slides, we wanted to compare the reproducibility of our results and identify the contribution of run-to-run variation to the observed variability.…”

Section: Resultsmentioning

confidence: 90%

Elucidating Spatially-Resolved Changes in Host Signaling During Plasmodium Liver-Stage Infection

Glennon

Tongogara

Primavera

et al. 2022

Front. Cell. Infect. Microbiol.

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Upon transmission to the human host, Plasmodium sporozoites exit the skin, are taken up by the blood stream, and then travel to the liver where they infect and significantly modify a single hepatocyte. Low infection rates within the liver have made proteomic studies of infected hepatocytes challenging, particularly in vivo, and existing studies have been largely unable to consider how protein and phosphoprotein differences are altered at different spatial locations within the heterogeneous liver. Using digital spatial profiling, we characterized changes in host signaling during Plasmodium yoelii infection in vivo without disrupting the liver tissue. Moreover, we measured alterations in protein expression around infected hepatocytes and identified a subset of CD163+ Kupffer cells that migrate towards infected cells during infection. These data offer the first insight into the heterogeneous microenvironment that surrounds the infected hepatocyte and provide insights into how the parasite may alter its milieu to influence its survival and modulate immunity.

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Section: Resultsmentioning

confidence: 90%

Elucidating Spatially-Resolved Changes in Host Signaling During Plasmodium Liver-Stage Infection

Glennon

Tongogara

Primavera

et al. 2022

Front. Cell. Infect. Microbiol.

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“…in both HepG2 cells and mouse liver, has been identified as a host kinase that upregulates numerous cell cycle genes. It plays an essential role in liver-stage parasite development and was proposed as a potential drug target against drug-resistant malaria [ 55 ]. The host enzyme 5′ AMP-activated protein kinase (AMPK), a central regulator of cellular energy metabolism, undergoes modulation by P. chabaudi .…”

Section: Protein Ptms In Plasmodium Parasite Growt...mentioning

confidence: 99%

Post-Translational Modifications of Proteins of Malaria Parasites during the Life Cycle

Schwarzer,

Skorokhod

2024

IJMS

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Post-translational modifications (PTMs) are essential for regulating protein functions, influencing various fundamental processes in eukaryotes. These include, but are not limited to, cell signaling, protein trafficking, the epigenetic control of gene expression, and control of the cell cycle, as well as cell proliferation, differentiation, and interactions between cells. In this review, we discuss protein PTMs that play a key role in the malaria parasite biology and its pathogenesis. Phosphorylation, acetylation, methylation, lipidation and lipoxidation, glycosylation, ubiquitination and sumoylation, nitrosylation and glutathionylation, all of which occur in malarial parasites, are reviewed. We provide information regarding the biological significance of these modifications along all phases of the complex life cycle of Plasmodium spp. Importantly, not only the parasite, but also the host and vector protein PTMs are often crucial for parasite growth and development. In addition to metabolic regulations, protein PTMs can result in epitopes that are able to elicit both innate and adaptive immune responses of the host or vector. We discuss some existing and prospective results from antimalarial drug discovery trials that target various PTM-related processes in the parasite or host.

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Design and Antimalarial Evaluation of Polydopamine-Modified Methyl Artelinate Nanoparticles

Li,

Wang,

Han

et al. 2024

Mol. Pharmaceutics

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Targeted nanodrug delivery systems are highly anticipated for the treatment of malaria. It is known that Plasmodium can induce new permeability pathways (NPPs) on the membrane of infected red blood cells (iRBCs) for their nutrient uptake. The NPPs also enable the uptake of nanoparticles (NPs) smaller than 80 nm. Additionally, Plasmodium maintains a stable, slightly acidic, and reductive internal environment with higher glutathione (GSH) levels. Based on this knowledge, methyl artelinate (MA, a prodrug-like derivative of dihydroartemisinin) nanoparticles (MA-PCL-NPs) were developed using poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) by a thin-film dispersion method and were further coated with polydopamine (PDA) to obtain MA-PCL@PDA-NPs with a particle size of ∼30 nm. The biomaterial PDA can be degraded in slightly acidic and reductive environments, thereby serving as triggers for drug release. MA could generate reactive oxygen species and decrease GSH levels, consequently causing parasite damage. The in vitro release experiment results indicated that the cumulative release

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STK35L1 regulates host cell cycle-related genes and is essential for Plasmodium infection during the liver stage of malaria

Cited by 4 publications

References 38 publications

Elucidating Spatially-Resolved Changes in Host Signaling During Plasmodium Liver-Stage Infection

Elucidating Spatially-Resolved Changes in Host Signaling During Plasmodium Liver-Stage Infection

Post-Translational Modifications of Proteins of Malaria Parasites during the Life Cycle

Design and Antimalarial Evaluation of Polydopamine-Modified Methyl Artelinate Nanoparticles

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