Modulation of host cell SUMOylation facilitates efficient development of <i>Plasmodium berghei</i>
 and <i>Toxoplasma gondii</i>

Maruthi, Mulaka; Singh, Dipti; Reddy, Segireddy Rameswara; Mastan, Babu S.; Mishra, Satish; Kumar, Kota Arun

doi:10.1111/cmi.12723

Cited by 15 publications

(15 citation statements)

References 37 publications

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“…Host-cell invasion and cyst genesis has been related to the SUMOylation mechanisms in Toxoplasma (Braun et al, 2009 ), as well as in other parasitic protozoa such as Plasmodium (Issar et al, 2008 ) and Trypanosoma (Shang et al, 2009 ). Moreover, modulation of the host SUMOylation machinery have been as well linked to both Plasmodium and Toxoplasma for efficient infection (Maruthi et al, 2017 ). Taken together, our data could suggest a SUMO/ubiquitination mechanism not only relates to the invasion process but as a way to transform/assimilate host proteins before the sporont maturation.…”

Section: Discussionmentioning

confidence: 99%

Comparative Time-Scale Gene Expression Analysis Highlights the Infection Processes of Two Amoebophrya Strains

et al. 2018

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Understanding factors that generate, maintain, and constrain host-parasite associations is of major interest to biologists. Although little studied, many extremely virulent micro-eukaryotic parasites infecting microalgae have been reported in the marine plankton. This is the case for Amoebophrya, a diverse and highly widespread group of Syndiniales infecting and potentially controlling dinoflagellate populations. Here, we analyzed the time-scale gene expression of a complete infection cycle of two Amoebophrya strains infecting the same host (the dinoflagellate Scrippsiella acuminata), but diverging by their host range (one infecting a single host, the other infecting more than one species). Over two-thirds of genes showed two-fold differences in expression between at least two sampled stages of the Amoebophrya life cycle. Genes related to carbohydrate metabolism as well as signaling pathways involving proteases and transporters were overexpressed during the free-living stage of the parasitoid. Once inside the host, all genes related to transcription and translation pathways were actively expressed, suggesting the rapid and extensive protein translation needed following host-cell invasion. Finally, genes related to cellular division and components of the flagellum organization were overexpressed during the sporont stage. In order to gain a deeper understanding of the biological basis of the host-parasitoid interaction, we screened proteins involved in host-cell recognition, invasion, and protection against host-defense identified in model apicomplexan parasites. Very few of the genes encoding critical components of the parasitic lifestyle of apicomplexans could be unambiguously identified as highly expressed in Amoebophrya. Genes related to the oxidative stress response were identified as highly expressed in both parasitoid strains. Among them, the correlated expression of superoxide dismutase/ascorbate peroxidase in the specialist parasite was consistent with previous studies on Perkinsus marinus defense. However, this defense process could not be identified in the generalist Amoebophrya strain, suggesting the establishment of different strategies for parasite protection related to host specificity.

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Section: Discussionmentioning

confidence: 99%

Comparative Time-Scale Gene Expression Analysis Highlights the Infection Processes of Two Amoebophrya Strains

et al. 2018

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“…SMAD4 Cignal-GFP reporter assay was performed in podocyte cells, according to the earlier published protocols with minor modifications 51 . Briefly, podocyte cells in a 96-well plate, 1000 cells/well were seeded before the day of transfection.…”

Section: Methodsmentioning

confidence: 99%

Growth hormone induces mitotic catastrophe of glomerular podocytes and contributes to proteinuria

et al. 2021

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Glomerular podocytes are integral members of the glomerular filtration barrier in the kidney and are crucial for glomerular permselectivity. These highly differentiated cells are vulnerable to an array of noxious stimuli that prevail in several glomerular diseases. Elevated circulating growth hormone (GH) levels are associated with podocyte injury and proteinuria in diabetes. However, the precise mechanism(s) by which excess GH elicits podocytopathy remains to be elucidated. Previous studies have shown that podocytes express GH receptor (GHR) and induce Notch signaling when exposed to GH. In the present study, we demonstrated that GH induces TGF-β1 signaling and provokes cell cycle reentry of otherwise quiescent podocytes. Though differentiated podocytes reenter the cell cycle in response to GH and TGF-β1, they cannot accomplish cytokinesis, despite karyokinesis. Owing to this aberrant cell cycle event, GH- or TGF-β1-treated cells remain binucleated and undergo mitotic catastrophe. Importantly, inhibition of JAK2, TGFBR1 (TGF-β receptor 1), or Notch prevented cell cycle reentry of podocytes and protected them from mitotic catastrophe associated with cell death. Inhibition of Notch activation prevents GH-dependent podocyte injury and proteinuria. Similarly, attenuation of GHR expression abated Notch activation in podocytes. Kidney biopsy sections from patients with diabetic nephropathy (DN) show activation of Notch signaling and binucleated podocytes. These data indicate that excess GH induced TGF-β1-dependent Notch1 signaling contributes to the mitotic catastrophe of podocytes. This study highlights the role of aberrant GH signaling in podocytopathy and the potential application of TGF-β1 or Notch inhibitors, as a therapeutic agent for DN.

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“…Cell growth, differentiation, response to stress, regulation of signal transduction, gene expression, and chromatin remodeling, among others, require SUMOylation of certain proteins [ 9 , 10 ]. In protozoan parasites, it is known that SUMOylation takes part in cell-cycle progression and influences morphology in Giardia lamblia [ 11 ], while in Trypanosoma brucei , it contributes to chromatin organization [ 12 ] and in Plasmodium falciparum , participates in invasion [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Protein Sumoylation Is Crucial for Phagocytosis in Entamoeba histolytica Trophozoites

Díaz-Hernández

Javier-Reyna

Sotto-Ortega

et al. 2021

IJMS

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Posttranslational modifications provide Entamoeba histolytica proteins the timing and signaling to intervene during different processes, such as phagocytosis. However, SUMOylation has not been studied in E. histolytica yet. Here, we characterized the E. histolytica SUMO gene, its product (EhSUMO), and the relevance of SUMOylation in phagocytosis. Our results indicated that EhSUMO has an extended N-terminus that differentiates SUMO from ubiquitin. It also presents the GG residues at the C-terminus and the ΨKXE/D binding motif, both involved in target protein contact. Additionally, the E. histolytica genome possesses the enzymes belonging to the SUMOylation-deSUMOylation machinery. Confocal microscopy assays disclosed a remarkable EhSUMO membrane activity with convoluted and changing structures in trophozoites during erythrophagocytosis. SUMOylated proteins appeared in pseudopodia, phagocytic channels, and around the adhered and ingested erythrocytes. Docking analysis predicted interaction of EhSUMO with EhADH (an ALIX family protein), and immunoprecipitation and immunofluorescence assays revealed that the association increased during phagocytosis; whereas the EhVps32 (a protein of the ESCRT-III complex)-EhSUMO interaction appeared stronger since basal conditions. In EhSUMO knocked-down trophozoites, the bizarre membranous structures disappeared, and EhSUMO interaction with EhADH and EhVps32 diminished. Our results evidenced the presence of a SUMO gene in E. histolytica and the SUMOylation relevance during phagocytosis. This is supported by bioinformatics screening of many other proteins of E. histolytica involved in phagocytosis, which present putative SUMOylation sites and the ΨKXE/D binding motif.

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Modulation of host cell SUMOylation facilitates efficient development of Plasmodium berghei and Toxoplasma gondii

Cited by 15 publications

References 37 publications

Comparative Time-Scale Gene Expression Analysis Highlights the Infection Processes of Two Amoebophrya Strains

Comparative Time-Scale Gene Expression Analysis Highlights the Infection Processes of Two Amoebophrya Strains

Growth hormone induces mitotic catastrophe of glomerular podocytes and contributes to proteinuria

Protein Sumoylation Is Crucial for Phagocytosis in Entamoeba histolytica Trophozoites

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